While investigating a haunting in an abandoned asylum and rescuing two teenagers who ventured in, Sam and Dean become trapped with the spirits of those who had died in a riot decades ago, one of which was a doctor who causes extreme rage in his victims.
Sam and Dean investigate an abandoned sanitarium and discover that when the hospital was open, the patients held a revolt against the cruel and unusual experimental treatments carried out by the head doctor. Now the ghosts roam the halls, driving anyone who spends the night insane. While trying to rescue two lost teenagers, Sam is captured and turns against Dean.
In Rockford, Illinois, while investigating possible trespassers in the South Wing of the Roosevelt Hospital, two policemen find a group of teenagers drinking in the place. One of the policeman drives insane and kills his wife, committing suicide immediately after. Dean receives a message in his cellular with the coordinates of the asylum, and drives with Sam to the place. The brothers disclose that the patients riot against the director, Dr. Ellicott, who conducted painful and cruel experiments with the patients and his body has never been found. Further, that there is a local legend that any person that spend the night in the asylum, the spirits drive he or she crazy. Together with Kat and Gavin, a young couple that is trapped in the Asylum, Dean and Sam spend the night in the cellar of the South Wing trying to find the hidden body of Dr. Ellicott to burn it and destroy the fiend.
- Teenagers break into an empty former asylum in Rockford, Illinois on a dare, as legend says that angry spirits of former patients occupy the place, and are caught by the police. Later that night, one of the cops goes home and kills his wife, and then himself.
Elsewhere, Sam () and Dean () continue their search for John (), calling several of his known associates with no luck. Dean is surprised to receive a text message, which he assumes to be from John. He finds that the numbers in the message are coordinates for Rockford, and when he finds the news story about the policeman and finds mention of the old asylum in John's journal, he concludes that it is a mission and that John wants he and Sam to investigate. Sam thinks their time would be better spent finding their father, but Dean, used to following John's orders, says they have to work the case. They travel to Rockford and question the policeman whose partner killed himself and learn that the man was a good cop with a normal life, suggesting that something in the asylum turned him suddenly violent. They explore the building, particular the south wing, going off of a note in John's journal about previous deaths that occurred there, and they find evidence of disturbing medical practices. Sam tries to convince Dean again to forget the case and go after John, but Dean refuses.
The brothers track down the son of the former chief-of-staff at the asylum, Dr. Ellicott, and Sam questions him about the south wing during a phony therapy session. Sam tells Dean that the south wing housed the most dangerous patients, and that there was a riot in the 1960s during which many people were killed, including Dr. Ellicott, and that several bodies were left unrecovered, meaning that the building is probably full of vengeful spirits that will be destroyed if the bodies are found and burned. Meanwhile, two more teenagers, Gavin and Kat, break into the asylum for fun, and Gavin is surprised and kissed by a ghoulish figure, much to his terror. Sam and Dean arrive and get wild readings on their EMF reader, and are quickly confronted by a spirit as well. Dean quickly shoots it with rock salt, but Sam points out that the ghost did not try to hurt him and clearly wants something else. They find Kat and Gavin, who tell them of their encounters, and Gavin says that his ghost tried to whisper something in his ear. As they move through the building, Kat is suddenly grabbed by a spirit and forced into a locked cell. Dean tries frantically to free her, but Sam encourages her to listen to the ghost and hear what it wants. Kat manages to calm herself enough to hear its whisper, and when they free her, she tells them that it said "one thirty-seven," which they take to refer to one of the rooms in the asylum. They attempt to help Gavin and Kat escape, but realize they are trapped by some force other than the patients that does not want them to leave.
In room 137, Dean finds Dr. Ellicott's old journals, which reveal some disturbing practices. Above, Sam receives a phone call from Dean telling him to come down to the basement, and leaves Kat and Gavin with a shotgun of rock salt for protection. When he goes to find Dean, however, he is grabbed by another spirit, which says it will make him "all better" and seems to send electrical shocks into him. Dean rejoins Kat and Gavin and says he never called Sam, and hurries off to the basement when he realizes that Sam was lured there by a spirit. He finds Sam, who appears to be fine, and explains that Dr. Ellicott was performing experiments on his patients and using rage therapy, but that it backfired and just made them more angry and violent. He guesses that the doctor's spirit is doing the same thing to anyone who enters the asylum, including the cop, and begins to search for the hidden room in which he performed his tests. Suddenly, Sam aims his gun at Dean, and Dean realizes he has been affected by the ghost. Sam shoots Dean with rock salt and rants at him about his blind obedience of John's orders, and Dean hands over his pistol and challenges him to shoot him for real. The gun is empty, however, and Dean overpowers him. He continues searching and finds Dr. Ellicott's corpse and prepares to torch it. He is attacked by the spirit, but manages to reach his lighter and burns the body, causing the ghost to disappear.
As they leave the asylum, Sam apologizes for what he said while under the doctor's influence, saying he couldn't control himself and didn't mean it. Dean shrugs it off, and they return to their motel. Early the next morning, Dean's phone rings again and Sam answers it--and it's John.