Steve Martin and Carl Reiner concoct one of Martin's best comic vehicles with Martin playing the world's top brain surgeon, Dr. Michael Hfuhruhurr -- he ought to know, he said so himself. Hfuhruhurr pioneered the radical new cranial screw-top technique, but he grieves over the untimely death of his wife Rebecca, carrying around a small plastic likeness of her to get through the long and lonely evenings. Thinking of her while driving home, Hfuhruhurr takes his eyes off the road and runs down the beautiful but deadly Dolores Benedict (Kathleen Turner). Hfuhruhurr performs surgery which saves her life, but as she recovers, Hfuhruhurr doesn't realize Dolores is a gold-digging vixen who has driven her latest husband (George Furth) to death by apoplexy. She is now looking for a new victim and Hfuhruhurr fits the bill. They marry, but Dolores denies her husband sexual favors, which frustrates Hfuhruhurr to distraction. He takes Dolores on a belated honeymoon to Austria, where he meets fellow brain surgeon Dr. Necessiter (David Warner), who keeps a wide assortment of brains in his laboratory. Dolores takes the opportunity to have an extramarital affair, and when Hfuhruhurr finds out he dumps her. But in Necessiter's laboratory, Hfuhruhurr becomes attracted to Brain #21, Ann Uumellmahaye (voice of Sissy Spacek), with whom he communicates telepathically. At last, here is one case where a man loves a woman for her mind rather than her body (which doesn't exist)! But Ann's brain is deteriorating rapidly; Hfuhruhurr needs to find a body and transplant the brain quickly in order to save Ann.