Roy Ashton's makeup for the creature included appliances created from a mold taken of real snakeskin.
Filmed simultaneously with The Plague of the Zombies (1966), from 13 September 1965 - 22 October 1965, reusing many of the same sets, most noticeably the main village set on the back-lot at Bray Studios. Dracula: Prince of Darkness (1966) and Rasputin: The Mad Monk (1966) were also filmed on many of the same sets in the same time period.
It was well known that Jacqueline Pearce, as documented in several books on "Hammer"'s history, disliked wearing the Reptile make-up as she suffers from claustrophobia. After this she vowed never to wear "creature" make-up in her future acting projects
Jacqueline Pearce said in an interview that she was called into a producer's office and told that she had a good face for movies. Then she was asked to play the titular character in The Reptile (1966). She could never understand that.
An actor named David Baron appears briefly in this film as the brother who dies at the beginning of the story. This same name was used briefly in the early 1950s by the unknown and unsuccessful actor Harold Pinter, who had reverted to his real name by the time he began to make his mark as a writer later in the decade. This coincidence led some, in later years, to make the entirely false assumption that Harold Pinter had acted in this Hammer horror film.