Although individuals with acquired immunodeficiency syndrome (AIDS) are often impaired on a variety of neuropsychological tasks, questions remain as to when neuropsychological decline can be reliably detected during the course of human immunodeficiency virus (HIV) infection. Detailed neuropsychological testing was accomplished on a cohort of 83 immunologically and neurologically intact asymptomatic HIV-infected individuals drawn from a larger pool of 649 US Air Force personnel with HIV antibodies. These asymptomatic subjects were compared with a group of HIV-negative subjects, and no significant differences in neuropsychological functioning were found. No significant neuropsychological differences were found as a function of cerebrospinal fluid abnormalities in these asymptomatic subjects. When data from 13 subjects with immune compromise were included in the analyses, those with abnormal cerebrospinal fluid values performed significantly poorer on a task of verbal memory, suggesting that cognitive dysfunction is antedated by immunological decline. Methodological problems that inhibit specification of the incidence, prevalence, and natural history of HIV-related cognitive impairment are discussed, as are data suggesting that previously published high estimates of the frequency of HIV-related dementia may not be representative of all HIV-infected populations.