Although this entire movie is about vampires, the word "vampire" itself is never actually used.
Originally, Jack Sholder was set to direct Lara Flynn Boyle and Dennis Hopper in the film. After Sholder backed out, due to creative differences, John Landis stepped in and replaced Boyle and Hopper with Anne Parillaud and Robert Loggia, respectively. Landis himself had been set to direct another vampire film for Warner Brothers and Joel Silver, called "Red Sleep", starring Wayne Newton as a Las Vegas lounge singer who is bitten and seduced by a female vampire. When the failures of Landis' L'embrouille est dans le sac (1991) and Silver's Hudson Hawk, gentleman et cambrioleur (1991) killed that project, Landis moved on to this movie. Landis told Filmmaker magazine in 2017, "I really liked [the script]. I was given tremendous freedom by the studio to make it, although it was rather low budget. It was very risky, which I think perhaps contributed to the fact that it didn't do well."
The distributors re-titled this film "A French Vampire in America" for international release without informing director John Landis, angering him and causing some confusion when the film was promoted outside the U.S.
Director John Landis said preview audiences had trouble understanding Anne Parillaud's heavy French accent, but he refused to dub her.
Le Fantôme de la rue Morgue (1954) is playing on the television during the morgue scenes, when Macelli is first brought in, and again when he makes his frenzied exit.
Steve Johnson, Tom Savini: Makeup effects artists have cameos in the film. Johnson as a hospital orderly and Savini as a press photographer.
Linnea Quigley, Steve Johnson: Scream Queen as a nurse. Her husband shares a scene with her as an orderly.
John Landis: [filmmakers] Appearances by directors Dario Argento, Frank Oz, Sam Raimi, and Michael Ritchie; "Famous Monsters of Filmland" Editor Forrest J. Ackerman; and Make-up Artist Tom Savini.
John Landis: [See You Next Wednesday] Advertised on the marquee across the street from the Melody Lounge exotic dance bar. The car crash at the Shadyside gas station scene was filmed in Squirrel Hill, and the nearby multiplex cinema changed its marquee to be "See You Next Wednesday" every night after closing. The movie itself featured no footage of that theater (or the street it's on), although it's possible that it was edited out.