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Professor Jonathan Drake remains haunted by his belief that a curse has been placed on the male members of his family by the South American Jivaro Indian tribe that he has studied all his life. When the professor learns that his brother Kenneth has found a Jivaro shrunken head at his home, he immediately wires that he will come visit. That evening, however, Zutai, a Jivaro, kills Kenneth with a poisonous bamboo blade, but Zuati's attempt to severe his head is interrupted by the butler, Rogers. The following day, police detective Lt. Jeff Rowan calls at Kenneth's home and informs Rogers that he has been contacted by Jonathan's anxious daughter Alison. Rogers reveals that Kenneth died the night before and takes Jeff to the attending doctor, Dr. Bradford. Bradford confirms that Kenneth died a natural death, then introduces Jeff to Dr. Emil Zurich, an archaeologist, summoned by Bradford when Rogers found the shrunken head. The next morning, Zutai secretly watches the arrival of Kenneth's body for the funeral service, and enters the house unobserved. A little later, Jonathan arrives and is shocked to learn of his brother's death. Bradford, present for the service, assures Jonathan that Kenneth died naturally, but Jonathan insists on opening the casket. The men are stunned when they find Kenneth's head has been removed from his body. Meanwhile in a basement laboratory at Zurich's house, Zurich and Zutai prepare Kenneth's head for the complicated shrinking procedure. Alison arrives at Kenneth's to look after her distressed father and meets with Jeff, who informs her that the mutilation of Kenneth's body has made the death a police matter. After recovering from his shock, Jonathan apologizes to Alison for his lifelong obsession with the family curse and announces it is time she learned the truth. Jonathan takes Alison to the burial crypt where four generations of male Drakes lie, where he tells her that his great grandfather, sea captain Wilfred Drake, had a trading station in the upper Amazon. When the local Indians kidnapped Wilfred's Swiss agent, he took an expedition to rescue him, but upon finding the agent's decapitated body at a Jivaro village, Wilfred ordered all the male Indians slaughtered. Only the village witch doctor remained alive and he cursed Wilfred's male heirs. Jonathan then opens a cabinet where he shows a horrified Alison the two skulls of his grandfather Gilbert and his father David, both of whom died inexplicably at the age of sixty and whose heads were mysteriously removed, then later returned to the vault. Back at Zurich's laboratory, the scientist successfully removes Kenneth's skull which he orders Zutai to place in the Drake crypt. Alarmed by her father's belief that he will be the next to die, Alison contacts Jeff and repeats her father's story, then shows him the vault. Although skeptical, Jeff explores the crypt and both and he and Alison are startled when they open the cabinet and discover three skulls. Unknown to the couple, Zutai has slipped into the house where he attacks Jonathan with the poisoned bamboo blade, but is forced to flee when Rogers appears. Jeff and Alison witness Zutai's escape and Jeff fires his pistol at him. Bradford is summoned to try to save the paralyzed Jonathan, but is unable to make a diagnosis. Jeff takes a blood sample to the police lab where technician Lee Coulter's analysis reveals the poison curare. Bradford quickly makes up an antidote, saving Jonathan's life. Jeff orders a guard for the Drake home, then takes Coulter into the Drake crypt to dust for fingerprints on the newly arrived skull. The men are astonished when the prints reveal the outline of a tiny human skull on each fingertip. With Bradford and Alison's help, Jeff examines books in Kenneth's library and discovers that skulls engraved on the fingertips is a practice associated with Jivaro witch doctors. The books also reveal the Jivaro legends that witch doctors could gain immortality by particular customs. Later, while walking around the house, Jeff and Alison discover a moccasin and one of Jeff's bullets embedded in a tree. Jeff takes the objects to Coulter whose examination reveals that the bullet has strong traces of curare and the moccasin is made from human flesh. After Zurich and Zutai conduct a native ceremony that results in Jonathan experiencing visions of skulls and a sense of his impending death, Bradford orders the agitated professor sent to the hospital. Bradford then visits Zurich and relates his theory that Kenneth died from curare poisoning. Bradford is taken aback upon discovering that Zurich knows that Jonathan is still alive. Zutai then kills Bradford and takes his body to his lab. Soon after, Jeff visits Zurich to consult with him about the Jivaro culture. Zurich explains that headhunting continues to exist in many native cultures, many of whom believe that taking the head of an enemy bestows the dead's spirit and immortality upon the head taker. Jeff's departure spurs Zurich to hurry his attack on Jonathan and he and Zutai head to the Drakes'. Jeff calls Coulter to ask him to run a check on Zurich, then reveals he noticed a strange stain on the scientist's rug, which he intends to examine. After Zurich departs, Jeff sneaks into the house and examines the stain, which appears to be blood. Beneath the rug, Jeff finds a trap door leading to the bizarre laboratory and finds Bradford's decapitated head. At the Drakes', Zutai is confounded when he finds Jonathan's room empty, but Zurich learns from Rogers that Jonathan has been sent to the hospital. Leaving Zurich's lab, Jeff phones Coulter who excitedly tells him that he has learned Zurich was a Swiss trading agent nearly two hundred years ago. Meanwhile, Zurich calls Jonathan to tell him that he is holding Alison hostage. Taking a cab home to verify that Alison is missing, Jonathan gets a pistol and goes to Zurich's home, where confronts the scientist, telling him he knows Zurich is an immortal, with his head sewn onto a Jivaro native body. Jonathan then threatens to shoot himself, which would break the Drake curse and transfer it to Zurich. Horrified, Alison and Zurich try to stop Jonathan. Jeff arrives and is attacked by Zutai, who inexplicably vanishes when the detective throws him into a fire. After Zurich flees the lab, Jonathan gives Jeff the bamboo blade, with which he attacks and paralyzes the scientist. Alison and Jeff then watch as Jonathan removes Zurich's head from the Indian body, thus giving both souls eternal rest.