As a child Mike Blueberry (Vincent Cassel) is dropped off in an isolated Western town Palomito by his fed-up father. His uncle (Tchéky Karyo) owned a ranch in the town and Mike is supposed to work as a ranch hand to earn his keep. The brute's only 'motivation' is a stick.There the teen-aged Blueberry falls in love, but his girlfriend Madeleine (Vahina Giocante) is a town prostitute. She is killed during a shootout with an evil man named Wally Blount (Michael Madsen), who barges in on their love making session. Mike manages to escape on Wally's horse.Blueberry flees into Indian territory. A Chiricuahua (Apache) medicine man's family finds, nurses and initiates him. The medicine man finds Mike covered with snakes and unharmed. Intrigued, he takes Mike under his care. Mike is taken to a cave.He is given Peyote; this causes him to trip heavily, and ultimately gain an entirely new perspective on life.With time, his wounds heal as well. Mike learns the Indian way of life, living with the tribe in the mountains. Indians raise Blueberry, teaching his their ways and their mystical powers. He is now accepted as one of their own, fully conversant with their customs and traditions. With time, the medicine man dies. Mike is returned to his own people.As an adult Blueberry becomes a U.S. Marshall, and as such attempts to broker peace between the whites and Indians. Jimmy McClure (Colm Meaney) is his deputy. Rolling Star (Ernest Borgnine) is the sheriff in town.The whites have heard those mountains are filled with gold and are looking for any reason to enter them.Maria (Juliette Lewis) runs the town ranch. Maria is Greg's (Geoffrey Lewis) daughter, who runs the town Saloon.Mike attempts are thrown into conflict, though, when Blount turns up looking for "gold." In fact he's searching for the substance that turned on Blueberry, and will stop at nothing to get it.Wally harasses an Indian woman Runi (Temuera Morrison) to find the manuscript that divulges the location of the sacred mountain, that is supposed to have the Peyote. Runi says that Prosit (Eddie Izzard) already took the manuscript.Woodhead (Djimon Hounsou) is working for Prosit. When confronted by Indians, Prosit left Woodhead behind to escape.Prosit cuts his own head before he enters the town saloon. He shows that as proof that Indians have attacked him unprovoked. Greg supports Prosit, but Mike wants to conduct a proper investigation.When Mike goes to the mountains, his Indian tribe attacks him for asking if they attacked Prosit. Mike is given proof of the white men (it was Woodhead's scalp) disturbing peace by entering the mountains.Blount and his men enter town in Mike's absence. Woodhead also makes it back to town alive, and his entire head has been scalped. Woodhead is about to shoot Porsit, when Blount intervenes and shoots Woodhead.Rolling Star arrests Blount and Prosit. Prosit tells Blount that Greg has the manuscript.Mike returns to town and asks Greg to keep away from the Indian territory. Mike goes to the station and realizes that Blount is Wally, who killed Madeleine. Mike goes home to get the revolver that Wally used to shoot Madeleine, but by the time he gets back, Wally is in charge of the police station, and he knows that Mike is the same guy he encountered all those years ago. Wally sets fire to the station, but Jimmy saves Mike by taking him to a hidden basement.Wally shoots Greg to get the manuscript. Maria launches her own escort to hunt Wally. Wally spares Prosit when he reveals that he ate the last 3 pages of the manuscript.Meanwhile Jimmy takes Mike to the Indians in the Mountains to get him treated. Mike is given Peyote again.Wally and his goons ambush Maria and her entourage and leave her for dead in the desert just outside the sacred mountains. Jimmy and Mike find them while returning from the sacred mountains.Mike and an Indian save Maria's like with Peyote.Prosit kills Wally's horse and heads for the Gold of the sacred mountain himself. Inside the cave, he is killed in quicksand trap.Blount heads for the same cave where Blueberry got his druggie induction, and there Blount finds a supply of Peyote.When Blueberry arrives, he finds he'll have to join Blount's hallucination in order to take him on. This leads to an otherworldly mind-war that takes these two back to their initial confrontation. Turns out Wally had shot Mike in the shoulder, and it was Mike who shot Madeleine in her head, causing her death.Maria enters the cave and kills Wally while he is under the influence of Peyote. Mike regains consciousness and realizes that he loves Maria.