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 quasi-sequel in 1968 entitled 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:
Orson Welles included a parody of Donovan's Brain in the The Orson Welles Almanac radio show broadcast a few weeks after his performance on Suspense.
The low-budget 1962 horror film, The Brain that Wouldn't Die features a severed head with a brain that learns to communicate telepathically.
The Brain, a disembodied brain in a glass vat, is a recurring supervillain in DC comics, head of the Brotherhood of Evil. He first appeared in the March 1964 issue of the Doom Patrol.
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.
The 1975 Doctor Who serial, The Brain of Morbius, starring Tom Baker, in which a scientist secretly preserves the brain of the renegade Time Lord, Morbius, in a fluid-filled tank, is based in part on - and the serial's title is directly inspired by - the movie "Donovan's Brain".
A 1978 episode of the TV show Wonder Woman entitled Gault's Brain features legendary horror film star John Carradine. He provides the voice for the vat-encased brain of a billionaire seeking a perfect physical specimen to be transplanted into.
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 1990 film Gremlins 2: The New Batch shows a scene in a genetics lab that pans past a brain in a jar labeled W. H. Donovan around 10 minutes into the film.
The 1998 Simpsons Hallowe'en special Treehouse of Horror IX contains a segment entitled "Hell Toupée". In the segment, Homer receives a hair transplant from recidivist criminal Snake which eventually possesses him, changing his voice and mannerisms and causing him to go on a crime spree.
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.
Siodmak's 1968 novel Hauser's Memory is a reworking of the basic idea. The RNA of a dead man is taken from his brain and injected into a scientist, who is then possessed by the dead man's memories and purposes. Although the story develops in a completely different direction, involving international intrigue, Siodmak places another Dr. Patrick Corey, with a similar cold-blooded personality, at the center of it. Despite this self-reference, it is not a true sequel, as this Corey is not old enough to have been the protagonist of Donovan's Brain and displays no memory of its events.