The authors compared the nature and severity of substance disorder (SD) in patients with mental retardation (MR) compared with SD in non-MR patients. Subjects were patients sequentially admitted to alcoholism/addiction programs in two university medical centers (MR + SD = 40; SD-only = 308). Data were collected on demographic characteristics, substance use history, SD duration and severity, and family history of SD. Subjects with MR + SD began substance use at a later age, used fewer substances during their lifetime (especially illicit substances), used less frequently in the past year, had lower severity scores on measures of substance abuse severity, and demonstrated milder and briefer substance use histories. It appears that less substance abuse is required in MR than in non-MR persons to precipitate psychosocial crises and health problems associated with psychoactive substances.