OBJECTIVE To evaluate changes in T-cell subsets in prevalent human immunodeficiency virus type 1 (HIV-1) seronegative and seropositive intravenous drug users (IVDUs) and in HIV-1 seropositive IVDUs with known time of seroconversion. METHODS Cohort study with a median 18-month follow-up. METHODS Community-based clinic established to study the natural history of HIV infection in IVDUs. METHODS Eight hundred fifty-nine self-referred IVDUs aged 18 through 49 years who injected drugs within the last 10 years and who did not have an AIDS (acquired immunodeficiency syndrome)--defining illness; 152 were seronegative for HIV-1, 621 were seropositive, and 86 seroconverted during the study. METHODS Proportions and absolute numbers of lymphocytes and CD3, CD4, and CD8 T cells as determined at 6-month intervals by flow cytometry and complete blood cell counts with automated differential. RESULTS Median numbers of CD4 lymphocytes at enrollment were 1061/microL (1.06 x 10(9)/L) for seronegative IVDUs, 508/microL for seropositive IVDUs, and 733/microL for those who seroconverted (enrolled a median of 4.5 months after seroconversion); the corresponding figures for CD8 lymphocytes were 628, 894, and 889/microL, respectively. Median rates of decline in absolute numbers and percentages of CD4 lymphocytes per 6 months were 7.6/microL (0.0%) for seropositive IVDUs and 55.1/microL (1.9%) for IVDUs who seroconverted (median follow-up after seroconversion was 12 months). Multivariate regression analysis that incorporated the within-individual correlation of the CD4 lymphocyte counts showed no significant change in these cells over time and no change due to use of drugs. CONCLUSIONS Our data suggest that progression of HIV-1 infection in IVDUs, as reflected in decline of CD4 cell counts, is no more rapid than that reported for other risk groups.