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Physician and scientist Patrick J. Cory and his wife Janice bring home a monkey for use in Patrick's brain experiments. Inside their home laboratory, Pat and his partner, alcoholic surgeon Frank Schratt, achieve their first success in keeping the monkey's brain alive outside of its dead body. Jan, a nurse, monitors the brain after sheriff's rangers call the doctors to the site of a small plane crash. Frank and Pat transport the victim, renowned multi-millionaire Walter H. Donovan, to the house for emergency care. After Donovan dies despite their best efforts, Pat is inspired by the idea of removing Donovan's brain for his experiment. Ignoring Jan and Frank's protests against the illegal procedure, Pat removes the brain, places it in a liquid solution and connects it to an oscillograph to monitor brain wave activity. Donovan's body is remanded to a local hospital and although Pat and Frank are relieved when no autopsy is ordered, Pat is forced to defend Frank against accusations by administrators that he is not fit to perform surgery because of his drinking. Pat later reluctantly allows news photographer Herbie Yocum to photograph the laboratory where Donovan died. Pat soon becomes obsessed with Donovan's brain, and while Frank is away, Jan helps him monitor the brain's activity. After a week, Pat notices that the brain absorbs nourishment and is growing in size. When Jan expresses concern that Pat's obsession with the experiment is causing their relationship to suffer, Pat affectionately reassures her of his love. Pat then hooks up the oscillograph to a sound monitor so he can hear the brain waves. Frank, dismissed from his hospital job, returns to the lab and moves in with the couple. Frank's humorous comment that Pat will need a crystal ball to communicate with the brain inspires Pat to consider telepathy. The trio researches Donovan's life and learn that he had been a ruthless financier who was under investigation for tax fraud by the Treasury Dept. That night, Pat focuses all his attention on the brain. Around four o'clock in the morning, he goes into a trance and scribbles a note in Donovan's handwriting. Afterward, Pat realizes he has succeeded in making contact with Donovan. In time, Pat appears to be talking, walking and moving like Donovan, and Frank and Jan express their concern that he has lost control of the experiment. Pat refuses to relent, however, and, still under Donovan's influence, charters a plane to the city, where he stays in Donovan's favorite hotel. Herbie encounters Pat in the lobby and becomes suspicious when Pat goes to a bank and cashes a $27,000 check. The bank manager, who recognizes that the account's signatory is connected to Donovan, alerts the Treasury Dept. Pat orders a vast amount of scientific equipment for the laboratory, orders several suits made to Donovan's specifications and meets with Donovan's stunned attorney, Nathaniel Fuller, demanding that Fuller contact Donovan's secret Washington, D.C. cohort. When Fuller refuses because he cannot comprehend Pat's affiliation with Donovan, Pat threatens to incriminate Fuller in Donovan's tax fraud investigation if he refuses to cooperate. Later that day, Treasury agents Brooke and Smith question Pat, but he steadfastly refuses to provide any information. Herbie then blackmails Pat by threatening to publish an article titled "Dead Man's Living Brain," complete with photographs of the laboratory. Donovan's grip on Pat barely wavers when he returns home exhausted, and he immediately sets up the delivered failsafe equipment that is designed to keep the brain alive. Frank fears that Pat will soon lose his own personality completely and attempts to shut off the power to the brain while Jan and Pat are asleep. Donovan's brain awakens Pat, however, and he attempts to strangle Frank. Jan intervenes in time to save Frank's life, but Pat still refuses to end the experiment. Back in the city, Pat meets with Fuller and his Washington connection, who states that since Donovan's death, he has agreed to cooperate with the government's investigation. Pat demands his loyalty and vows to continue to pay the man off as Donovan had arranged. After they leave, Pat suffers extreme physical pain and his own personality takes over. Because he cannot reach Jan by telephone, he makes a tape recording of instructions for her, referring to the lightning rod on their house as a method to stop the machinery. He then leaves the hotel but, seeing that he is being followed and unable to otherwise rid himself of Donovan's influence, Pat purposely steps in front of an oncoming truck. Pat suffers only a mild injury and has a few moments as himself before Donovan's brain takes over again. Donovan's son and daughter later confront Pat and after admitting that they loathed their vicious father, ask Pat to stop his activities on their dead father's behalf. Pat is unmoved and reveals that he has arranged for them to be disinherited. When Herbie demands more money, Pat suggests that he drive to the house to take more photos, then calls Frank to tell him to leave Herbie alone in the laboratory. There, the brain puts Herbie in a trance that results in a fatal car crash. Pat checks out of the hospital and initiates a frenzy of activity during which he cashes numerous checks, pays off Fuller and secretly arranges for a special vault to house Donovan's "remains." Pat is completely consumed by Donovan's thought processes and now becomes suspicious of Frank and Jan, who are planning to disconnect the brain from the equipment. When Pat arrives at the house, Jan takes him for a stroll in spite of an impending thunderstorm. When Jan tells him the experiment is over and delays their return to the house, he starts to strangle her. At that moment, Frank shoots the brain and Pat appears to be released from its influence. The brain is still engaged, however, and forces Frank to turn the gun on himself. Pat and Jan run to the house where Pat, still under the influence, insists that Jan stare at the brain. At that moment, lightning strikes the rod, which is hooked into the power supply, causing power to go out and engulfing the brain in flames. Some time later, Brooke arrives to pick up Pat and Frank, who was injured but not killed. Now that Pat's personality has been restored, he is eager to take responsibility for his actions, and he and Frank are cooperating with the government to help mitigate the charges against them.