We determined intrathecal synthesis (ITS) of anti-HIV-1 immunoglobulin in 62 CSF samples from 51 HIV-1 seropositive homosexual men using an ELISA technique with paired serum and CSF samples diluted to a concentration of IgG of 10 micrograms/ml. All subjects were neurologically normal and none was taking zidovudine. We estimated duration of HIV-1 infection from semiannual serologic testing during the 3-year period before CSF analysis and detected ITS of anti-HIV-1 immunoglobulin in 2 of 12 (17%) of those with less than 18 months of HIV-1 seropositivity, in 3 of 21 (14%) with 19 to 36 months, and in 13 of 29 (45%) with greater than 36 months of HIV-1 seropositivity (p = 0.037). There was a trend toward an inverse relationship between level of ITS and the peripheral blood T-helper lymphocyte count. This study demonstrates that increasing ITS of anti-HIV-1 IgG is related to duration of HIV-1 infection and suggests an inverse correlation with systemic immune status. The detection of ITS of anti-HIV-1 immunoglobulin is not necessarily a marker of clinically overt neurologic involvement.