Grace Zabriskie said on Sheryl Lee's performance in the film: "She gave everything she had, she gave more than she could afford to give, and she spent years coming back".
According to writer Robert Engels, he and director David Lynch originally conceived this film as the first in a series of films exploring the mythology of the Black Lodge. To that effect, the two inserted four characters as "outs" with which to continue the story: Agent Dale Cooper (Kyle MacLachlan), Agent Phillip Jeffries (David Bowie), Major Garland Briggs (Don S. Davis), and Agent Chester Desmond (Chris Isaak). However, the critical and box-office failure of this film caused Lynch to abandon any plans for sequels.
Richard Beymer (Ben Horne) declined to participate due to a scene where Ben was to force Laura to kiss him in exchange for a bag of cocaine. Beymer felt that there had been no buildup for the character of Horne (who confesses his love for Laura in Twin Peaks (1990)) to extort Laura, and that as a result the scene came off as exploitative. As a result, another scene, in which Leland Palmer (Ray Wise) confronts Ben about Laura's photo being on Ben's desk, resulting in a fight with Ben's wife, was never shot. The scene also would have included Johnny and Jerry Horne.
In retrospect, David Lynch has said, "I feel bad that Fire Walk with Me did no business and that a lot of people hate the film. But I really like the film. But it had a lot of baggage with it. It's as free and as experimental as it could be within the dictates it had to follow."
In most versions of the film, certain sequences are subtitled - at the nightclub where the music drowns out the dialogue and when characters speak backward - but not in the British version. Apparently, Director David Lynch changed his mind so often as to whether they should be included or not, by the time he came to a final decision, the British distributors had already made all their prints (without subtitles) and couldn't afford to make any more.
David Lynch: [Sunset Blvd.] Lynch's character Gordon Cole is named after an oft-mentioned character from Sunset Boulevard (1950).