The novel became an instant classic and was adapted for the big screen three times. Since then the book has become something of a cult classic, with fans including Stephen King, who discussed the novel in his 1981 book Danse Macabre. Siodmak later wrote a sequel in 1968, titled, Hauser's Memory.
The novel is written in the form of diary entries by Dr. Patrick Cory, a middle-aged physician whose experiments at keeping a brain alive are subsidized by Cory's wealthy wife. Under investigation for tax evasion and criminal financial activities, millionaire megalomaniac W.H. Donovan crashes his private plane in the desert near the home of Dr. Cory. The physician is unable to save Donovan's life, but removes his brain on the chance that it might survive, placing the gray matter in an electrically charged, oxygenated saline solution within a glass tank. The brainwaves indicate that thought—and life—continue. Cory makes several futile attempts to communicate with it. Finally, one night Cory receives unconscious commands, jotting down a list of names in a handwriting not his own—it is Donovan's. Cory successfully attempts telepathic contact with Donovan's brain, much to the concern of Cory's occasional assistant, Dr. Schratt, an elderly alcoholic.
Gradually, the malignant intelligence takes over Cory's personality, leaving him in an amnesiac fugue state when he awakes. The brain uses Cory to do his bidding, signing checks in Donovan's name, and continuing the magnate's illicit financial schemes. Cory becomes increasingly like the paranoid Donovan himself, his physique and manner morphing into the limping image of the departed criminal. Donovan's bidding culminates in an attempt to have Cory kill a young girl who stands in the way of his plans. Realizing he will soon have no control over his own body and mind, Cory devises a plan to destroy the brain during its quiescent period. Cory resists the brain's hypnotic power by repeating the rhyme "He thrusts his fists against the posts and still insists he sees the ghosts." With Dr. Schratt's help, he destroys the housing tank with an ax and leaves the brain of Donovan to die, thus ending his reign of madness.
The idea of a disembodied brain controlling people - as well as the novel's title and quotations from it - have been referenced several times since the book's publication. Some notable examples include:
- The low-budget 1962 horror film, The Brain that Wouldn't Die features a severed head with a brain that learns to communicate telepathically.
- A reference to the title can be found at the end of Larry Niven's 1965 short story "Becalmed in Hell," in which the character Eric, who lives as a brain and spinal cord on life-support, and works as the directly connected controller of a NASA exploratory vessel, signs a telegram, "Donovan's Brain."
- The September 1968 episode of Star Trek, "Spock's Brain" features the disembodied brain of Mr. Spock kept alive in a box attached to a control panel.
- Another influence that can be seen is in an episode[which?] of the 1960s TV series The Avengers. The mind of an evil genius is kept alive by repeatedly taking control of the mind and body of victims, a feat which is accomplished with the assistance of a mad scientist doctor and nurse. The evil genius uses mind control (along with a computer-like contraption that keeps his brain alive in his otherwise dead body) and amplifies the power of his brainwaves to control other people.
- As mentioned above, novelist Stephen King discusses Donovan's Brain in his non-fiction book Danse Macabre, (1981) and the line Cory uses to resist Donovan is used to similar effect in King's horror novels Salem's Lot (1975) and It (1986).
- In the 1983 film The Man with Two Brains, the protagonist Dr. Michael Hfuhruhurr (played by Steve Martin) claims that the film adaption of Donovan's Brain is his favorite film and later discovers a colleague who is able to keep brains alive in jars. Hfuhruhurr subsequently falls in love with one of the brains.
- The Beastie Boys use the line from the novel, "He thrusts his fist against the post and still insists he sees the ghost" in their song "Dropping Names" on the album 1989 Paul's Boutique.
- The character of Uncle Irving in the 1995 fantasy film The City of Lost Children is a talkative brain in a tank.
- The title is satirized in the February 2001 episode of the TV series Big Guy and Rusty the Boy Robot, called "Donovan's Brainiac", where the nephew of Dr. Donovan uses the brain of the Legion Ex Machina's Number Five in a robot he built for a science fair.
The 1976 Doctor Who episode "The Brain of Morbius" involves the brain of an evil Time Lord kept alive by artificial means.
- Orson Welles on Suspense Archive.org hosts MP3 recordings of the 1944 radio version.
- Radio adaptations of Donovan's Brain on Suspense