In the Ink and Paint Club, when Jessica is about to do her number, just as the curtains open, her dress snaps off for a split second, then reappears. This can only be seen in slow motion on the laserdisc version, however.

After filming, Bob Hoskins had hallucinations, and his son became angry at him for not bringing any of his cartoon friends home.

Another scene of Jessica's exposure can be found when Benny the cab crashes into the lamp-post after sliding through the puddle of dip. She and Eddie are thrown from the car, and spin around. As Jessica spins, she is seen to have no panties on. This is only visible on the original VHS and Laserdisc versions. On the DVD, fabric from her dress has been added to cover the exposure.

When the filmmakers sought permission to use the Looney Tunes characters in the film, Warner Brothers only agreed on the condition that Bugs Bunny receive equal screen time with Mickey Mouse.

In early versions of the script, Judge Doom had a pet vulture and was the one who shot Bambi's mother.

The film's credits run for nearly ten minutes. At the time of its release, Who Framed Roger Rabbit held the record for having the longest end credits sequence in cinema history.

The title has no question mark at the end, because according to director Robert Zemeckis, there's an old superstition that films with a question mark in the title do badly at the box office.

Ever wonder what all that technical jargon that Judge Doom rattles off about his "Dip" was all about? The Dip, which he tells Eddie is a mixture he has made out of acetone, benzene, and turpentine, is the only way to kill a toon. Why? Because these are essentially the three main ingredients in "Paint Thinner" - which he uses to literally remove a toon's paint, thereby removing their existence.