Christian Slater was given the role of Daniel Malloy upon the death of River Phoenix, the original choice for the role. Slater donated his $250,000 salary to two of Phoenix's favorite charities.
Anne Rice wrote Lestat in the 1976 novel with Rutger Hauer in mind. The rights to the novel were optioned by Paramount for $150,000 before the book was published, and John Travolta was earmarked to play Lestat, but a glut of vampire films at the time with Dracula (1979), Nosferatu the Vampyre (1979), and Love at First Bite (1979) put the project on hiatus. By the time the film was in preproduction, Hauer and Travolta had become too old to portray the ever-young vampire (ironically, Hauer would later portray a vampire in both Buffy the Vampire Slayer (1992) and Salem's Lot (2004)). Upon learning that Tom Cruise had been cast, Rice was livid and stated Cruise could not carry the part, calling the casting "so bizarre; it's almost impossible to imagine how it's going to work" and "the worst crime in the name of casting since The Bonfire of the Vanities (1990)." Rice recused herself from the production and did not view the film until a producer sent her a VHS copy. Rice was so impressed by Cruise's performance that she wrote him a letter of apology and recorded a two-minute video endorsing the film that was included as a pre-feature on mid-1990s VHS releases of Interview with the Vampire.
All the actors playing vampires were required to hang upside down for up to thirty minutes at a time during make-up. This would force all the blood in their bodies to rush to their heads, causing the blood vessels in their faces to bulge. The make-up artists would then trace over the swollen veins, creating the eerie, translucent-skinned look. Unfortunately for the actors, they would have to repeat the process several times over, as the blood would quickly drain from their heads. This, in part, accounts for the lengthy make-up process.
Anne Rice was so pleased with this adaptation that she took out a two-page ad in both Vanity Fair and the New York Times, endorsing it as "a masterpiece."
In an EW interview in September 2011, Brad Pitt revealed that he had a miserable experience while making this film. He recalled the discomfort of the makeup, colored contacts and particularly filming in an enclosed dark indoor area. He said at one point he called his friend and producer David Geffen and begged him for a way out. Learning that it would cost $40 million, he toughed it out for the remaining months.