In the cartoon, Mickey is hooked on a Mortal Kombat-style video game based on Snow White and the Seven Dwarfs when Minnie comes home to find that Mickey forgot their anniversary. Mickey comes up with a last-minute idea to take her to a miniature golf course. Showing her a newspaper, Minnie misinterprets and thinks Mickey is taking her to Hawaii, a trip that would cost $999.99, one penny short of $1000. An excited Minnie skips out the door before Mickey can set her straight, causing Mickey to worry about how to earn so much money. Pluto shows his master the "help wanted" ads, and Mickey finds an ad for work with a Dr. Frankenollie (an inside joke reference to Disney animators Frank Thomas and Ollie Johnston) for a day of "mindless work" that would instantly give him $999.99.
Mickey goes to the home of the simian Dr. Frankenollie (voiced by Kelsey Grammer). When he knocks the door, Mickey gets sucked downward through a trap door into Frankenollie's laboratory, where Frankenollie plans to switch Mickey's brain and soul with that of his monster, Julius (portrayed by perennial nemesis Black Pete). Although Dr. Frankenollie is killed in the experiment, the brain transfer is a success, with Mickey's mind ending up in Julius' giant body and Julius finding himself in control of Mickey's body.
The dimwitted and insane Julius finds Mickey's wallet in his pocket and, finding a photo of Minnie, is instantly smitten with her. He escapes the laboratory on a hunt for Minnie, whom he finds shopping for a bathing suit. When the real Mickey (in Julius' body) shows up to save his girlfriend, Minnie screams for help and runs until Mickey convinces her of who he is. Julius continues to pursue Minnie, leading to a battle between the two of them ("Go get him, Mickey!" cheers Minnie, "Rip his ears off!").
During the course of their battle, Julius and Mickey fall onto electric wires, which cause their minds and souls to transfer back to their correct bodies. Although Julius is more of a threat than ever now that he is again in control of his own monstrous body, Mickey manages to subdue him and save Minnie. The closing scene of the film finds Mickey and Minnie on their way to Hawaii, with Julius providing the horsepower for their inner tube.
- Wayne Allwine as Mickey Mouse
- Russi Taylor as Minnie Mouse
- Kelsey Grammer as Dr. Frankenollie
- Jim Cummings as Julius
- Bill Farmer as Pluto
When the film was first being pitched, Dr. Frankenollie's role was played by Professor Ecks from Floyd Gottfredson's Mickey Mouse comic strip storyline Blaggard Castle, though studio executives didn't go for it and the new character was created.
After the theatrical runs of A Kid in King Arthur's Court, A Goofy Movie and George of the Jungle, Disney kept Runaway Brain out of circulation because of its use of an "evil Mickey" character and the darkly comedic death of the professor.
Home video releases
- Mickey's Greatest Hits
- Walt Disney Animation Studios Short Films Collection (Disney Movies Anywhere Debut/Exclusive)
In other media
- Julius appears as an optional secret boss in Kingdom Hearts 3D: Dream Drop Distance in Traverse Town.
- Zazu makes two cameos in the short.
- When the video-game Dopey is killed, the "Wilhelm scream" is heard.
- On Mickey's wall is a poster with a picture of a mousetrap, labeled Just Say No.
- Julius finds a black & white picture of Mickey from Steamboat Willie in Mickey's wallet. (to which Mickey comments, "Oh, that's old.") During the end credits you also hear a modern Hawaiian-themed version of the tune from that particular cartoon.
- Mickey's arrival at Dr. Frankenollie's street is a parody of the famous poster image from the film, The Exorcist.
- This is so far the only theatrical Mickey Mouse short where Jim Cummings voices Pete, since in the 2013 short Get a Horse!, his voice was provided by archived audio clips of Billy Bletcher or Will Ryan.
- As Mickey is falling down the trap-door chute, a pink-slip with the initials "J.K." is glimpsed fluttering down the chute with him. This is a reference to the firing of Jeffrey Katzenberg from the Disney corporation just the previous year.
- Runaway Brain was also planned to be attached to 101 Dalmatians but was pulled out of theaters at the last minute so that trailers for Hercules, That Darn Cat, Jungle 2 Jungle, and George of the Jungle could play instead.
- Mickey seems to playing the video game on a Sega Genesis.
- The short's presentation on the Mickey Mouse in Living Color, Volume 2 DVD set has a slight audio sync problem. It is currently unclear if this is fixed on the Walt Disney Animation Studios Short Films Collection DMA digital copy.
- This movie was mentioned in Epic Mickey when Oswald asks Mickey for more confessions, which he doesn't have any. Oswald then lists some things, one being "brain-swapping". Even though Mickey took part in it, he didn't have the idea to do it.
- For an unknown reason, the restored Disney Movies Anywhere-exclusive digital version of this short film strangely used the 2011 Miramax logo at the beginning (followed by the retained 1995 Walt Disney Pictures logo) and the closing Miramax logo at the very end. (Miramax was formerly owned by Disney from 1993 to 2010.)
- However, as of October 12, 2017, the Miramax logo has been removed from the Movies Anywhere release of the short, typically correcting the error.