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This paper presents five case studies of persons who were mentally retarded prior to infection with human immunodeficiency virus (HIV). Particular emphasis is placed on neuropsychological functioning, and its interaction with management and treatment. The effects of HIV on neurological functioning in such persons has not been previously documented. Although it may be hypothesized that mentally retarded people are at increased risk for developing neurological complications, these preliminary data suggest this is not so and that the development of HIV-related encephalopathy is no different in the mentally retarded, manifesting in the AIDS-related complex (ARC) and AIDS stages of illness. Within the context of HIV infection, the cognitive status of the mentally retarded creates unique treatment and management difficulties, and some guidelines are presented.