The Man with Two Brains tells the story of Dr. Michael Hfuhruhurr, a brilliant brain surgeon who, after saving the life of Dolores Benedict, a gold-digging femme fatale, falls in love and marries her. However, their marriage turns out to be loveless, as Dolores is only interested in Michael's money. While on a honeymoon and business trip to Vienna, Michael meets Dr. Alfred Necessiter, a mad scientist who has developed a technique for storing living brains in liquid-filled jars. Michael discovers that he can communicate telepathically with one of the brains, that of Anne Uumellmahaye, and the two fall in love. Dolores, jealous and angry, attempts to kill Anne by putting her brain in an oven, but Michael intervenes and literally tosses Dolores out of his house. Michael consults with Necessiter about transplanting Anne's brain into a new body but ultimately decides to use a syringe filled with window cleaner (the same substance used by the serial killer known as the "Elevator Killer") to end Dolores' suffering and make way for his new love interest with Anne. The film explores themes of love, marriage, infidelity, and the ethical implications of brain transplants; it is a sci-fi comedy-romance that will keep the audience engaged until the very end.

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Some movies that have similar genres and were produced around the same time as The Man with Two Brains include Spaceballs, Brazil, Attack of the Killer Tomatoes!, Critters 2, Leonard Part 6, A Midsummer Night's Dream.

The Man with Two Brains was released in theaters on June 10, 1983.