In the small town of Pontypool, Ontario, former shock jock turned radio announcer Grant Mazzy drives through a blizzard on his way to work. When poor visibility forces him to stop his car, an underdressed woman appears on the road, startling him. Grant calls out to her, but she disappears into the storm, ominously repeating his words and visibly disturbing him. Grant eventually arrives at the radio station, where he works with technical assistant Laurel-Ann Drummond and station manager Sydney Briar.As the morning proceeds, Grant's on-air persona irritates Sydney. They get a report from their helicopter reporter Ken Loney (which Sydney reveals to Grant is a man on a hill with sound effects mimicking a helicopter) about a possible riot at the office of a Dr. Mendez. He describes a scene of chaos and carnage that results in numerous deaths. After Ken is unexpectedly cut off, the group tries to confirm his report, but their witnesses are disconnected before they can put them on the airwaves. Ken calls back and reports that he has found the "infected" son of a well-known citizen nearby, who is mumbling to himself. Before Ken can hear what the son is saying, the call is again cut off, this time by a startling transmission of garbled French.The transmission is an instruction to remain indoors, not to use terms of endearment, phrases that conflict, or the English language. Pontypool is declared to be under quarantine. Ken then manages to call back, this time close enough for Grant and the women to hear the infected son's mumbling, which is nothing but "Mommy" in a child's voice. In confusion and disbelief, Grant tries to leave the station, but a horde of people attack, and Grant, Sydney, and Laurel-Ann lock themselves in. Meanwhile, Laurel-Ann begins demonstrating erratic behavior. She fixates on the word "missing," repeating it over and over, then imitates the sound of a boiling kettle. Dr. Mendez enters the studio and Grant, Sydney, and Mendez lock themselves in Grant's soundproof booth.Mendez explains his theory: somehow a virus has found its way into human language, infecting certain words, and only certain words infect certain people. Once these infected words are said and understood, the virus takes hold of the host. As he explains, Laurel-Ann repeatedly slams against the sound booth's window, chewing off her lower lip and splattering blood with each attack. Ken calls in again and, while on the air, he also succumbs to the apparent virus, repeating the word "sample."Outside the booth, Laurel-Ann opens her mouth and vomits a large amount of blood and gore before falling down, dead. Mendez suspects this has happened since Laurel-Ann failed to pass the infection on to a new host. The horde then breaks into the radio station, attacking the sound booth. Sydney records a loop of Grant saying "Sydney Briar is alive" and plays it over the station's outdoor loudspeaker as a diversion to lead the mob away. Dr. Mendez begins to repeat the word "breathe" but immediately begins speaking in Armenian, which stifles, but not eliminates, the symptoms. Mendez surmises that it is only the English language that was affected by the virus. Grant and Sydney, speaking in French, leave him alone in the booth. They are nearly killed when the recording fails and the mob returns, but Mendez successfully lures them away from the studio.Feeling guilty for killing an infected young girl, Sydney begins to succumb to the word "kill". Grant then attempts to "disinfect" Sydney by convincing her that the word "kill" now means "kiss". He urges her to repeat "Kill is kiss" over and over again, and her symptoms subside. She tells Grant to "kill" her; he then proceeds to kiss her. Armed with knowledge on how to stop the virus, the pair go on the air, spouting a series of non-contradicting and confusing phrases to help their infected listeners, ignoring warnings from the authorities who are trying to get them off the air. While an amplified voice from outside counts down from ten, Sydney joins Grant in the booth and they kiss once again. As the countdown finishes, the screen goes dark and the credits roll.Audio vox pops and broadcasts play over the credits, reporting further outbreaks of the virus, suggesting that the quarantine failed. After the credits, the scene shifts to a radically different view: a stylized black-and-white version of Grant and Sydney in what looks like a far-eastern atmosphere. As Grant describes his plan to "get out of here", the picture gradually shifts into color.