We compared rates of progression to AIDS for 99 injection drug users and 120 homosexual men with documented dates of HIV-1 seroconversion. The crude risk of developing AIDS was higher among homosexual men than injection drug users [relative hazard (RH) = 2.4; 95% confidence interval (CI) = 1.3-4.4]. The relative hazard was slightly smaller among participants with a seroconversion interval of < or = 1 year (RH = 2.2; 95% CI = 1.0-5.2). The effect was partially explained by the inclusion of Kaposi's sarcoma in the AIDS case definition. Excluding those with Kaposi's sarcoma, the relative hazard was 2.0 (95% CI = 1.1-3.8). Using the 1993 AIDS case definition decreased the effect (RH = 1.9; 95% CI = 1.1-3.4). Finally, the high pre-AIDS mortality among injection drug users could partially explain the difference in progression rate between injection drug users and homosexual men. Combining the effect of the above-mentioned factors resulted in a relative hazard of 1.3 (95% CI = 0.7-2.6). Thus, the slower progression to AIDS among injection drug users compared with homosexual men was largely explained by differences in the spectrum of AIDS-defining illnesses, pre-AIDS mortality, and length of seroconversion interval.