Gene Wilder went to the NY League for the Hard of Hearing to study for his role. There he was assigned to speech pathologist Karen Webb, who would ultimately become his fourth wife.
Gene Wilder almost wasn't in this movie. Per his autobiography, he turned the script down twice (due to its treatment of the deaf and the blind). He intended to do the same when offered it a third time, but his agent talked him into meeting with TriStar Pictures (the studio behind the film). The TriStar people asked Gene to re-write the script for him and Richard Pryor, which he agreed to do.
Kevin Spacey has a protruding cyst on his left cheek in the movie. This is not a feature of his character, but a real cyst that needed to be removed in a surgical procedure.
To prepare for his role, Richard Pryor went to Braille Institute in Los Angeles, where he was taught "cane technique" (the correct way a person who is blind uses a white cane) and visited classrooms to observe mannerisms of the blind students.
Gene Wilder initially felt uneasy doing the film, despite the producers making changes to accommodate him and Pryor. He was worried the film would mock people with disabilities, but started to change his mind when, during research and meeting with real deaf people, he was told, "people with handicaps do have a sense of humor." While the film inevitably upset some people, he was encouraged by letters from people saying they thought it was a nice change to see people with disabilities as the heroic central characters, as opposed to being mere background characters.