We have studied cerebrospinal fluid obtained from 38 homosexual or bisexual men participating in a prospective study of the neuropsychological disorders associated with human immunodeficiency virus (HIV) infection. Twenty-two subjects had neuropsychiatric findings and seropositivity, 11 asymptomatic subjects had seroconverted within 6 to 24 months, and 5 subjects were seronegative controls. Only 1 had acquired immunodeficiency syndrome-related complex, and none had the acquired immunodeficiency syndrome when initially studied. There was a high rate of cerebrospinal fluid abnormalities in men with neuropsychiatric findings, including pleocytosis (41%), elevated IgG and IgG index (47%), and oligoclonal bands (18%). Even in the absence of neuropsychiatric findings, the asymptomatic HIV-seropositive subjects frequently had spinal fluid abnormalities. Of those with neuropsychiatric findings, HIV p24 antigen was detectable in cerebrospinal fluid in only 1 individual, yet HIV was isolated in 11 of 16 (69%) compared to 2 of 7 (29%) of those without neuropsychiatric findings. The identification of cerebrospinal fluid abnormalities in individuals known to have become infected within 6 to 24 months supports the hypothesis that the nervous system is an early target for HIV.