To investigate whether predictors of AIDS progression are operative very early in the natural history of HIV infection, we conducted a nested case-control study within a cohort of 119 subjects who seroconverted while under observation in a prospective study of homosexual men. For each of the 18 cases who have progressed to AIDS, we randomly selected three controls who had seroconverted within 3 months of the case but who have remained AIDS-free. Cases and controls were compared with regard to laboratory and clinical parameters obtained at the time of the earliest HIV-positive result. The median duration between the estimated date of seroconversion and this first positive result was 4 months for cases and 6 months for controls. Cases exhibited lower CD4 counts (657 versus 774 x 10(6)/l; P = 0.037), lower CD4: CD8 ratios (0.98 versus 1.39; P = 0.003), higher immune complex levels (C1q binding: 25 versus 15%; P = 0.002), lower hemaglobin concentrations (14.8 versus 15.2 g/l; P = 0.011), higher immunoglobulin (Ig) A levels (272 versus 184 mg/dl; P = 0.003), and higher IgG levels (1530 versus 1300 mg/dl; P = 0.037) than controls. Cases exhibited higher CD8 counts of marginal statistical significance (732 versus 597 x 10(6)/l; P = 0.059). No differences were observed with respect to IgM levels, total lymphocyte or white blood cell counts, or the frequency of generalized lymphadenopathy. A total of 27.8% of cases but only 11.5% of controls reported one or more symptoms during the 6-month period preceding the first positive visit (P = 0.027). We conclude that laboratory and clinical abnormalities which are predictive of more rapid progression to AIDS may appear very early in HIV infection. This suggests that some of the factors responsible for more rapid disease progression are present in the host prior to or shortly after infection occurs.