For the past two years, New York City has been in the grip of an epidemic: Strickler's Disease is threatening to wipe out an entire generation of the city's children. Efforts to find either a vaccine or a cure have failed. But there is some hope in the recent discovery that the common cockroach is responsible for spreading the disease. Dr. Peter Mann (Jeremy Northam), of the Center for Disease Control, enlists the aid of Dr. Susan Tyler (Mira Sorvino), a noted entomologist. She develops a new species of insect she calls the Judas Breed, genetically engineered to secrete an enzyme that poisons normal cockroaches, and die off without reproducing within 180 days. Six months later, at a press conference, Dr. Mann announces that the epidemic is officially over. Peter and Susan are now married, and hope to start a family soon. Susan still has some misgivings about manipulating the DNA of the Judas Breed, but Peter assures her they did the right thing.On a rainy night three years later, in a run-down church in a Lower Eastside neighborhood, a preacher (Pak-Kwong Ho) is attacked and flees to the roof of the building. His assailant, a tall, thin man in a long overcoat, follows. The preacher jumps onto a painter's scaffold rigged to the side of the building, to escape; the ropes break and he falls to his death in the alley below. After a few moments, his body is dragged roughly into a nearby storm drain. A ten-year-old autistic boy, Chuy (Alexander Goodwin), watches dispassionately from the apartment building across the alley where he lives with his father, Manny (Giancarlo Giannini). Chuy imitates the clicking sounds the attacker made with a pair of spoons. Repeating "funny, funny shoes" to himself, he begins to bend a scrap of wire into a small figure.Next morning Peter arrives at the church. Police officers checking on the broken scaffold have discovered a large group of illegal immigrants locked up in the basement, all infected with yellow fever. The CDC will need to set up a quarantine and investigate. As Peter and his assistant Josh (Josh Brolin) look through the seedy old church, they come across a nasty surprise in a basement passageway: Several large clumps of feces fastened to the ceiling, and hanging down from it, like stalactites. Peter is concerned, since there is a connection between the basement passageways and the subway tunnels. Josh collects a sample for analysis; later, he shows Peter one of the bizarre components found in the sample: buttons...regular buttons...from human clothing.That afternoon, Susan is working in her lab with her assistant, Remy (Alix Koromzay). They are approached by a couple of twelve-year-old boys (James Costa and Javon Barnwell). Susan has a standing offer to pay the neighborhood kids for any unusual bugs they find, and these two have brought her a number of specimens...including a very unusual one, taped up in a cornflakes box. She offers them $10 for everything; they accept it and leave. Remy leaves shortly after, by the rear exit where her bike is parked. She bumps into a tall, thin man in an overcoat in the alley, mumbles an apology and slips on past him.Susan puts on a pair of surgical gloves and extracts the bug from the cornflakes box with a pair of forceps. Large and unique, it nevertheless appears to be just a baby. She reaches to examine it with her other hand...it bites her, latching ferociously onto the web of skin between her thumb and index finger. Startled, she pulls it off roughly, jams it down onto a pin board, and stabs a large pin into it to hold it there. She takes off the gloves and is checking for damage to her hand when she notices the bug is secreting a large amount of frothy liquid...like the Judas Breed. She searches through her files on the creation of the Judas Breed...she finds a litmus test strip made from the secretions...she compares it side by side with a test strip from the new bug. They are identical.She hears glass breaking...the lamp that was shining on the baby bug has been knocked to the floor, and the nearby window is open. When she investigates, she finds the bug is gone. She gets down on the floor to search for it, unaware she's being watched...by a tall, thin intruder clinging effortlessly to the ceiling above her. When she stands up, there is a sudden gust of wind, a shadow moves...and she is alone.Peter is shaken and angry when he hears of the incident. He asks Susan to cut back on the hours she spends alone in her lab at night. Her concern, however, is the Judas Breed. If it's still alive and reproducing, there's no telling what long-term impact it could have. She convinces Peter that they need to investigate further.Next day, the boys take Peter, Susan and Remy into the subway, to the place where they found the bug. They wind up outside a locked door, marked "Private", which the boys claim wasn't locked the day they went through it. Susan gives them a picture of an ootheca, an egg sack, and asks if they've seen anything like it. They haven't...but want to know what she'll pay if they find one. Remy hustles them away, telling them their dealing days are over. Peter and Susan pick the lock on the door, and enter what looks like an abandoned locker room. Their search is interrupted by a Manhattan Transit Authority officer, Leonard (Charles Dutton), who threatens to arrest them both. Peter convinces him they are there on official CDC business, but Leonard stubbornly insists that Peter will need to come back with the proper permits before he'll let him in to look around. Peter vows to do so, and also vows he will request Leonard to be assigned as their personal escort through the maintenance grid tunnels for being so obstructive.Susan waits on the subway platform while Peter and Leonard argue, leaning against one of the pillars, tapping her foot. She notices Chuy, nearby, imitating her tapping with his spoons. When she walks over to say hello and engage him in conversation, he merely remarks, "Lace-up shoes...black...Nine West," the style, color and manufacturer of the shoes she is wearing. He goes back to sit near Manny, who operates a shoeshine stand there on the platform. She watches, interested, as Chuy continues to imitate the tapping sounds made by all the people walking by and names the shoes each is wearing. She sees some of his wire sculptures, which are really quite good, and she tells him so. He holds up the one he made most recently, that looks very much like the specimen she had in her lab the night before: "Mr. Funny Shoes", he says. Susan asks Manny why Chuy doesn't go to school...Manny simply shrugs, and responds, "He doesn't have to: he's special."The two young boys have gone back into the subway tunnels to look for an ootheca. Transients, camped on the landings in this deserted part of the subway, warn them not to go any further. "Long John," they call after the boys, "Overcoat Slim...Don't go down there, or he'll getcha!" The boys fling a few insults back at them, and ignore their advice. They find what they're looking for, in a remote part of the tunnel: an ootheca the size of a gym bag. But they find "Overcoat Slim" there, too, keeping watch. He catches first one, then the other...and kills them quickly and brutally.Susan goes to talk with an old professor/mentor, Dr. Gates (F. Murray Abraham). She tells him what's happened, and asks if he thinks it's possible some of the Judas Breed bugs survived...he tells her he thinks it's likely. "But they were engineered to die," she says, plaintively, "in the lab, they all died." "Yes, Susan, but you let them out of the lab, " he replies. She asks if he still thinks it was wrong to do what she did. He tells her three years earlier he would have called it unforgivable. But he adds kindly that now, with two healthy grandchildren probably alive only because of her work, it would be hypocritical for him to pass judgment.Late that night, Chuy is watching the deserted church from his bedroom window...He sees the tall, thin man go inside. Gathering up his spoons and his bent wire figures, he crawls out the window and goes down the fire escape. The door of the church is boarded up, but he's small enough to fit through the gaps. Inside, he hears Mr. Funny Shoes clicking away, and imitates him with his spoons. Mr. Funny Shoes answers, and Chuy responds happily. Then there are more clicks...a second Mr. Funny Shoes is in the room. Chuy continues to "talk" to both of them...but as they move in closer, flanking him on either side, his facial expression changes from delight to fear.Next morning, Remy calls Susan and tells her to meet her at a sewage treatment plant. A friend of hers who works there has found something strange. Peter reminds Susan they have the subway thing this morning; she tells Peter she'll have to meet him there after she checks on this lead.At the plant, Remy's friend produces a tray which holds the head, thorax and two sets of legs of an almost man-size insect. Remy takes pictures of the creature with her Polaroid camera, and Susan asks her to deliver the body to Dr. Gates for examination. Susan takes the pictures and goes to meet Peter at the subway.Manny discovers Chuy is missing. He remembers the boy's fascination for the church across the alley. He goes over there to look around, and sees one of Chuy's wire figures just inside the doorway. Armed with a Zippo lighter and an old-fashioned straight razor, he breaks into the church through a cellar door to look for Chuy.Leonard, Peter and Josh are making their way down through the subway access tunnels, and none of them are happy. They encounter another cluster of feces attached to the ceiling, take samples, and keep on moving. At last they find themselves on a high balcony, overlooking the old Armory Station. Leonard glances down and sees a large bug, like the one from Susan's lab. Startled and disgusted, he stamps on it, rendering it useless for identification and study. Peter is furious...he steps out onto the balcony near Leonard and they begin to argue violently. An ominous creaking sound makes them stop...the balcony beneath them collapses, and Peter and Leonard crash down to the floor below. They are not hurt, but there seems to be no way to climb back up...so Josh, who wasn't on the platform when it fell, is sent back to the upper level to bring help.Susan, waiting on the subway platform for Peter's return, has been studying the pictures that Remy took. She notices something, and starts creasing them, accordian-folding them to show certain parts of one side-by-side with another, and she realizes that the claws on the front pair of legs resemble a man's face when fitted together. She notices suddenly that it's late, and Peter has not come to meet her. She approaches the only other person on the platform, a tall, thin man in an overcoat, to ask if he has the correct time...he raises his head, and she sees it's a full-grown, man-size Judas adult! She turns to run, it unfurls its wings and flies after her, catching her and carrying her into the tunnel.Josh is still trying to find his way to the surface. He stumbles onto a nest of oothecas. A nearby Judas adult is roused, and comes after him...Josh is caught and killed as brutally as the two boys.Susan wakes up alone in an apparent cache of Judas victims--dead, partially consumed, rotting--and tries to find her way out. She falls through a manhole, and is discovered there by Manny, still looking for Chuy. Trying to find help for her, Manny stumbles onto Leonard and Peter. Together they rescue Susan from the manhole, but they are seen and pursued by a Judas adult. They are able to make it inside an old subway car, but the Judas adult also gets partly through the door. They force the door shut, cutting the Judas bug in half...still alive, the upper half falls into the car, and scuttles under a bench. Leonard shoots it, emptying a full clip from his gun into it. He reloads, and pulls it out from under the bench to examine it. Still alive, it slashes at his legs with its own lethal front legs, seriously injuring him with deep lacerations that bleed profusely. Leonard empties the second clip into it, finally killing it. But the scent of the blood attracts other Judas adults...they swarm over the car, ripping at it and buffeting it. Susan borrows Manny's razor and cuts into the dead adult, extracting its scent glands. They smear the secretions over any cracks in the windows and other openings. The Judas adults withdraw from the car, apparently fooled by the scent.Leonard tells the others that they are in a Coney Island Special car that may still be operable. It might be possible for them to escape if they can restore the power. Peter volunteers to go out and check the power line. Manny volunteers to go out and throw the track switch, which will give him a chance to search a little longer for Chuy. Leonard and Susan will start the car and pick up Peter and Manny at a point further down the track. Susan smears the secretions from the two scent glands on them to increase their chances of survival.Peter is able to find and repair the circuitry. Manny finds the track switch, and miraculously, also finds Chuy nearby. For unknown reasons, Chuy has been spared by the bugs, and apparently even believes they are his friends. He indicates as much to Manny, and shows no inclination to return with him. As Manny tries to coax Chuy to come along, a Judas adult descends from the ceiling, and tears Manny to pieces.Susan and Leonard are worried about Peter and Manny...it's been too long for them to be gone. Leonard is severely crippled because of the wounds on his legs...so Susan puts on the last of the scent from the dead adult and goes out to find them. Manny is gone...nothing left but blood and his crucifix. But Chuy is still there, terrified after witnessing the death of his father. Susan picks up Manny's crucifix, throws the track switch and takes Chuy with her to hunt for Peter.Peter has turned on the power, and the lights come on in the subway car. Leonard starts it up, but it only moves a few feet and lurches to a standstill. Peter returns to the car, but Leonard won't let him in. Leonard's wounds have begun to bleed again, and there is no more bug scent to mask the smell. The Judas adults are beginning to come back...Leonard is doomed, and he knows it. Peter reluctantly leaves him to go look for Susan. Leonard leaves the car, and heads down the track, to decoy the bugs away from the others. They swarm over him and kill him, but his sacrifice helps the others to avoid the bugs for a while, at least.The reunion of Peter, Susan and Chuy is brief. Peter persuades Susan to take Chuy and escape without him...he wants to try to wipe out the colony while he's here. If he fails, Susan will have to tell authorities what's happened and find another way to destroy them. He helps them into a dumb waiter/service elevator, and sends them up to the next level. The leader of the colony, the breeding male, crashes into the chamber at that moment, and Peter is forced to run through a tiny access tunnel into another large chamber. He slams the door behind him and looks around to see that he is in the main nursery of the colony, surrounded by thousands of oothecas and thousands more adults hanging from the ceiling beams watching over them. The chamber is half flooded with water, and there are gas pipes and valves all around. With an emergency fire ax, he cuts into several of them, venting gas into the chamber. The door bursts open, a couple of Judas adults swarm in...more are leaving their perches among the beams and flying toward him. With the ax, he strikes the metal grid to create a spark before they can reach him. On the third blow a spark ignites the gas, the chamber explodes in flame and Peter plunges into the water.Susan and Chuy have gotten out of the elevator, and they're standing in a track tunnel when they are knocked down by the explosion. Before they can recover, the breeding male, who has climbed up the elevator shaft, crashes into the tunnel at a point between them. He ignores Susan and turns to Chuy, intent on killing the boy. Susan slashes her palm with Manny's crucifix and holds it up so the male can scent the blood. The male turns and chases her instead. She hears a train coming, and runs directly toward it...at the last moment she jigs sharply to the side, and the train hits the male head on. Badly damaged, he clings onto the train, slipping partly underneath. As parts of him touch the ground they are torn away by the velocity, and at last, completely crushed and dismembered, he dies. Susan collects Chuy and they make their way up to the street.Later, they huddle in blankets on a bench outside the subway entrance. Dr. Gates approaches Susan, and tells her the fire department found no trace of the colony...nothing could have survived the fire. "How about one of us?" she asks, hopelessly. He touches her hand, and goes back to talk to the firemen. Chuy is watching as firefighters evacuate people from the subway. Something about his attitude catches Susan's attention, and she joins him at the top of the stairs. A tall man in a blanket is climbing slowly up the stairs. Chuy comments with satisfaction in his voice, "Mountain boots, size ten". The man looks up, and it is Peter. He climbs up the last few steps to them, opens his arms, and embraces them both.