Colin Clive's alcoholism had worsened since the first film, but James Whale did not recast the role because his "hysterical quality" was necessary for the film.
Cinematographer John Mescall presented a problem with his drinking, so serious the studio had to provide a car to get him safely to and from the set. Nevertheless, he was very good at his job, even when drunk, and James Whale liked that he worked fast and rarely wasted time fussing with incidental camera and lighting hardware.
Marilyn Harris, who played Maria, the girl The Monster accidentally kills in the original Frankenstein (1931), appears uncredited as another young girl. She is the leader of the group of young schoolgirls who encounter the Monster as he runs away from the blind man's burning house. Director James Whale deliberately gave her a one-word line ("Look!"), so she would be paid more by the studio as an actor with a speaking role, instead of as an extra.
Jack P. Pierce altered the make-up of Frankenstein's monster from this film's predecessor to reflect that he had survived the mill fire at the end of Frankenstein (1931) with some flesh burns and with much of his hair singed off.
Boris Karloff protested against the decision to make The Monster speak, but was overruled. Since he was required to speak in this film, Karloff was not able to remove his partial bridgework as he had done to help give the Monster his sunken cheek appearance in the first Frankenstein (1931). That's why The Monster appears fuller of face in the sequel.