The association between early virologic and immunologic events after human immunodeficiency virus type 1 (HIV-1) infection and progression of HIV-1 infection to acquired immunodeficiency syndrome (AIDS) was studied among 59 homosexual men with documented time of seroconversion. Epidemiologic factors, such as number of lifetime sexual partners, history of sexually transmitted diseases, and other factors, also were studied. All 17 seroconverters in the cohort who developed AIDS within 3 years (rapid progressors = RPs) were compared with 42 men without AIDS for at least 6 years seroconversion (nonrapid progressors = non-RPs). Plasma levels of HIV-1 RNA, p24 antigen, antibodies to HIV-1 structural genes, beta-2 microglobulin, neopterin, and interferon-alpha were measured at four time points: (a) the last seronegative visit, (b) the first seropositive visit, (c) the visit closest to AIDS (or the corresponding visit for the non-RPs) and (d) 6 years after seroconversion (for non-RPs). Up to seroconversion, the RPs had a significantly higher number of lifetime sexual partners than non-RPs (503 versus 171, respectively). At the first seropositive visit, RPs had significantly higher concentrations of plasma HIV-1 RNA (p < 0.01) and prevalence of p24 antigenemia (p < 0.001) and significantly lower levels of antibodies to the HIV-1 gag proteins p17 and p24 (p < 0.01-0.001) compared with non-RPs. These differences increased during follow-up visits. Antibodies to p66 and gp120 were significantly different only at the visit closet to AIDS (p < 0.001), as were beta-2 microglobulin and interferon alpha. These findings suggest that early virologic-immunologic events after HIV-1 infection may determine the rate of progression to AIDS. Anti-gag immune response may prevent rapid progression of HIV-1 disease and should be considered for future vaccine studies.