At a San Francisco, California, hospital, Dr. Bob McEvoy and tumor specialist Dr. Jack Hughes discuss an inexplicable, fast-growing swelling on the neck of McEvoy’s patient, Karen Tandy. The doctors schedule surgery to remove it but agree to keep quiet about the lump until they can explain it, since the tumor seems to have the characteristics of a growing human fetus. Elsewhere, fake psychic Harry Erskine gets a call from Karen, his ex-girlfriend, who asks to see him. When they meet, Karen tells Harry about the upcoming surgery for the growth on her neck and confides her belief that it is not just a tumor. At Harry’s home, he reads her tarot cards and the Death card keeps appearing. Harry and Karen make love and later, in the middle of the night, he hears her repeating a phrase in a foreign language in her sleep. The next morning, Harry asks Karen what she was saying but she does not know. Later, in the operating room, as Hughes prepares to make his first incision, Susan’s eyes open and she chants in a foreign language. A supernatural force compels the surgeon to cut his own wrist rather than the growth on Susan’s neck. Meanwhile, Harry ushers his next client, Mrs. Herz, into his apartment. The woman suddenly has a seizure and utters the same foreign words Karen said in her sleep. In a trance, she levitates out of the apartment and throws herself down the stairs. Later that day, Harry tells Hughes about his client’s strange behavior. He is worried that Karen’s life is in danger, but Hughes insists the mysterious words have no bearing on her medical condition. The surgeon admits he could not complete the surgery because Karen’s vital signs plummeted. He then explains that the swelling on her neck resembles a human fetus more than a tumor. Harry suspects something is trying to control Susan and is transmitting signals that are causing her condition. Later, Harry visits his mentor, Amelia Crusoe, at the occult shop she co-owns with her husband, “Mac” MacArthur. When Harry describes Karen’s condition, Amelia suggests they hold a séance. At the conclusion of the ritual, during which a ghostly head appears on the table, Amelia suggests they are dealing with an evil spirit that had knowledge of black magic when it was alive. Based on the figure they saw, Harry surmises it is the spirit of a Native American medicine man. Back at the occult shop, Harry, Amelia and Mac conduct research and learn there is a belief among Indians that a powerful medicine man’s immortal spirit, or Manitou, can be reborn by impregnating itself in a human host. When the three realize that Karen is about to give birth to such a being, they drive to Sausalito, California to consult an expert in Native American mythology, professor of anthropology Dr. Ernest Snow. Although Snow confirms the existence of reincarnated Manitou legends, he discounts the tales as folklore. Harry insists the myths must be real because Karen’s life is in danger. When Harry asks the professor if he recognizes Karen’s trance-like phrase, Snow identifies it as the language of a Northern California tribe that died out 400 years ago. Snow thinks the phrase means, “my death foretells my return.” The professor suggests that Harry travel to an Indian reservation in South Dakota to recruit a medicine man. Harry takes this news to Hughes, who alerts Harry that Karen is undergoing surgery at that moment. Since the scalpel failed before, the surgical team is trying to excise the growth with an optical laser. Just then, Hughes gets an urgent phone call and rushes down to the operating room with Harry where they learn that the laser whipped around on its own as the technicians attempted to make the first incision. Hughes and Harry see the laser incinerating objects in the operating room. The laser stops when Harry shuts off the power. Harry and Hughes cautiously enter the room and approach Karen. Speaking for the spirit growing on her, Karen intones that they must not touch him; the light has hurt him and he will kill them all. She screams and writhes until the hospital staff sedates her. Hughes conjectures that the spirit of the medicine man is afraid of the laser and X-rays. Later, Harry drives to a South Dakota Indian reservation and locates a medicine man named John Singing Rock. John informs Harry that the Manitou in question is gaining the strength of a Christ-like spirit called Gitche Manitou, the most powerful figure in the Indian belief system. Humans cannot defeat the Manitou, they can only send it back to the place from which it came. To banish the spirit without killing Karen, they will need to invoke the power of other spirits, such as the mountains or the wind. John agrees to help Harry for a $100,000 donation to the Indian Educational Foundation. In Karen’s hospital room, John draws a circle on the floor around Karen’s bed and cautions Harry and Hughes not to break or smudge the circle, since it is the only barrier that might contain the Manitou. As John begins his ritual, Karen awakens and speaks in the spirit’s voice, which calls itself Misquamacus and declares that it is stronger than John’s magic. Misquamacus warns John that if he helps the white men he will die. John explains that Misquamacus, the strongest medicine man of all, wants revenge. That night, Harry and John observe Misquamacus emerge from Karen’s back, then drop to the floor. As Misquamacus tries to break the circle, John calls on other spirits. Hughes wants to call the police, but John warns that Misquamacus can control the Manitous of manmade objects; if the police come, Misquamacus will turn the guns on the police just as the spirit turned the scalpel on Hughes. Later, Misquamacus breaks the circle and summons a lizard demon that bites Hughes on the hand. Harry takes Hughes to another floor for medical attention, then returns to Karen’s room where he discovers that Misquamacus has disappeared with Karen. John suspects the Manitou is opening a portal for a greater demon to enter the human world. Misquamacus reappears and tries to kill Harry and John, but Harry throws a typewriter at the spirit. Misquamacus destroys it, but John and Harry escape. John has beseeched every Manitou for help but none have been able to stop Misquamacus. Harry tells John it is time to call on Gitche Manitou. Just then, an earthquake erupts. When it settles, John explains that Misquamacus has summoned the Great Old One, an evil spirit akin to Satan, to help defeat the humans. Looking at the computer equipment, Harry suggests that John direct the energy of the hospital’s machines’ Manitous at Misquamacus. As he and Harry return to Karen’s room, John warns that the Great Old One is a master of illusion. Karen seems to float in outer space. John calls on the Manitous of the machines to send Misquamacus away and the building’s machines whirr to life, but since they were created by white men, they don’t respond to John. However, Harry’s love for Karen causes the Manitous to focus their power through her. Karen rises from the bed and emits bolts of energy from her fingertips that blast through Misquamacus. In retaliation, the Great Old One sends fireballs toward the humans, but with the aid of the machines, Karen destroys the demon. Once the room returns to normal, Harry and Karen embrace. The next day, John reminds Harry that Misquamacus’s body is dead, but the spirit lives on.