- The book next to the sleeping technician in the control room at the beginning of the film is "The Shape of Rage", an anthology of writings about the films of David Cronenberg, who directed this film's predecessor.
- John Getz (as Stathis Borans) is the only actor reprising a role from the original The Fly (1986).
- The first videotape of Seth Brundle (where he theorizes that the teleporter improved him) is actually part of a deleted scene from The Fly (1986). The scene was slightly edited for this film, and Veronica's (Geena Davis's) voice was dubbed over by Saffron Henderson (who plays Veronica at the beginning of The Fly II).
- The Telepod props from the The Fly (1986) were destroyed after filming was completed and were rebuilt.
- The green flashes of light between each credit in the title sequence were actually borrowed from an alternate, unused title sequence for The Fly (1986).
- In at least one draft of the script, Martin was going to see yet another videotape of Seth Brundle (this time nearing the end of his transformation), in which Seth talks about his "cure". This would have required brand-new footage of Jeff Goldblum in makeup from the previous film, and the concept was subsequently dropped from the script.
- The role of Martin Brundle was written for Eric Stoltz to play. He originally declined the role because he didn't like the script. When the script was rewritten, he accepted the part.
- An unusual trailer was made for the film that consisted of no footage, just an audio clip and the readout of a heart monitor.
- Vincent D'Onofrio was the first choice for the role of Martin Brundle and was nearly cast for the part but his screen tests didn't go well.
- In some US states, theaters playing "The Fly II" had a nurse on hand for the audiences' reactions to its content.
>>> WARNING: Here Be Spoilers <<<
Trivia items below here contain information that may give away important plot points. You may not want to read any further if you've not already seen this title.
- SPOILER: Geena Davis was offered the opportunity to appear in the film, but turned it down since Veronica Quaife was to be killed off very early on in the script, and had no real character development.
- SPOILER: The movie was originally given an X rating by the MPAA because of the graphic scene where Hargis' head is crushed underneath an elevator. Director Chris Walas appealed the decision, and the MPAA gave the film an R rating without any edits to the scene.
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