Since the movie was being made by Disney's Touchstone Pictures, Warner Bros. would only allow use of their biggest cartoon stars, Bugs Bunny and Daffy Duck, if they got as much screen time as Mickey Mouse and Donald Duck. For that reason, they were always in pairs, such as the piano battle between Daffy and Donald and the parachute scene with Bugs and Mickey. This was continued with Porky Pig and Tinker Bell at the movie's ending.
The dip that kills the toons is made of turpentine, acetone, and benzene, paint thinners used to remove images from cels.
Bob Hoskins said that, for two weeks after seeing the movie, his young son wouldn't talk to him. When finally asked why, his son said he couldn't believe his father would work with cartoon characters such as Bugs Bunny and not let him meet them.
This movie is the first (and only, as of 2024) time cartoon characters from Disney and Warner Bros. have appeared together on-screen.
When Eddie takes Roger Rabbit into the back room at the bar where Dolores works to cut apart the handcuffs, the lamp from the ceiling is bumped and swinging. Lots of extra work was needed to make the shadows match between the actual room shots and the animation. Today, "Bump the Lamp" is a term used by many Disney employees to refer to going that extra mile on an effect just to make it a little more special, even though most audience members will never notice it.