In a psychiatric hospital, Dr. Daniella Upton visits the morgue. There, the mortician dissects a corpse, the victim of a murder. Daniella visits the murderer, her friend Dr. Elizabeth Derby, who begs Daniella to destroy the corpse's brain. Derby begins to recount her story to explain why she must do so.
Psychiatrist Elizabeth Derby lives with her husband Eddie. After a session with a patient, a young man visits her office. He introduces himself as Asa Waite and claims that his father Ephraim is occasionally "using" his body. During the session, Asa receives a call from his father and appears to have a seizure before acting as if nothing happened, as well as behaving differently. Elizabeth is troubled by this development and that evening imagines Asa in Eddie's place while they are having sex. She goes to Asa's house and discovers Ephraim to be horribly sick, relying on pills to keep him alive. After Elizabeth spots a book with creatures and symbols drawn in it, Ephraim wards her off with a large knife.
That night, Asa calls Elizabeth and she drives to his house, finding Ephraim dying on the floor; Asa refuses to let Elizabeth hand him his pills but Elizabeth defies his orders, though she cannot stop Ephraim's apparent death. Asa tells her that they must destroy Ephraim's brain because if he says an incantation a third time, he will take over Asa's body. Ephraim utters the incantation, which causes Asa to have a seizure, before falling limp. Asa, now more confident, has sex with Elizabeth and whispers an incantation in her ear which causes them to briefly switch bodies. He notices that Ephraim's body is missing, prompting him to take the knife and chase after him. "Ephraim" begs Elizabeth to help him, claiming to be Asa trapped in the body. Ephraim, now inhabiting Asa's body, stabs Asa in the neck then decapitates him.
The following day, two detectives stop by the Derby residence to question Elizabeth about a fire at the Waite house, with Ephraim being labeled as a missing person. Elizabeth talks to her friend, fellow psychiatrist Daniella Upton, about the body-switch but Daniella does not understand what she means; later, Elizabeth admits her affair to Eddie. Meanwhile, Ephraim (still in Asa's body) handcuffs himself to a pole in his cellar and calls Elizabeth, reading the incantation and causing the two to switch bodies. While in Elizabeth's body, Ephraim has sex with Eddie; Elizabeth discovers piles of flesh as well as drawings of a creature in the cellar. Realizing that the next body swap will be forever, Elizabeth attempts to jump out of a window at her office but Ephraim arrives and says that she can escape if she kills him and destroys his brain. Upon distracting him, Elizabeth stabs him in the head with his knife before throwing him out of the window; realizing that he is still alive, Elizabeth runs Ephraim over repeatedly with her car before stabbing him to death. She is then apprehended by police officers.