Serum concentrations of interferon-gamma were measured in individuals seropositive for human immunodeficiency virus type 1 (HIV-1). According to the CDC classification system, 6 presented with stage IV-C, 5 with stage IV-A, 8 with stage III, and the remaining 24 individuals with stage II. A modified radioimmunoassay procedure for detection of interferon-gamma was used with a detection limit of 18 U/L. Approximately one-half (22/43) of the seropositives exhibited increased serum interferon-gamma concentrations compared with seronegative blood donors (n = 76). There was a significant association between serum interferon-gamma concentrations and CDC stages of the patients; patients classified as CDC IV-C had the highest concentrations. Further, a significant positive correlation was observed between serum interferon-gamma and serum neopterin concentrations in seropositive study participants. We conclude that interferon-gamma is present in increased concentrations in HIV-1 seropositives compared to seronegative blood donors. Diminished in vitro production of interferon-gamma by T-lymphocytes on stimulation with specific soluble antigens contrasts with increased levels of circulating interferon-gamma in patients.