Background: Comparisons of progression in HIV-1 infection between injecting drug users (IDU) and homosexual men have been inconclusive due to short follow-up periods, often with less well-defined starting points and endpoints. In addition, comparisons of survival after infection have been to some extent obscured by higher non-AIDS mortality in IDU. Methods: In a retrospective cohort study, homo-/bisexual men and IDU were followed, with dales of seroconversion defined within Il year by a previously negative HIV antibody lest. Endpoints were CD4 cell count below 200 x 10(6)/l, AIDS, and death from AIDS. Results: Sixty-three homo-/bisexual men and 125 IDU fulfilled the entry criteria, with no significant differences in age at or dale for seroconversion. Mean follow-up times were 6.7 and 7.0 years, respectively. The homo-/bisexual group had a significantly accelerated progression rate to all three endpoints: time to CD4 cell count below 200 x 10(6)/l (P = 0.002), to AIDS (P = 0.0003), and to death from AIDS (P < 0.0001). Adjusting for age and sex only made marginal alterations. Ten years after infection, 54% of homosexual men had developed an AIDS-defining condition and 51% had died from AIDS, whereas the corresponding percentages in the IDU group were 26 and 15%, respectively. There was, however, no difference in overall mortality due to an almost constant, non HIV-related, yearly mortality of some 4% in IDU. Conclusions: In our cohort there was a highly significant difference in disease progression and death from AIDS between homo-/bisexual men and IDU. This difference was proposed to be due to the transmission route determining the initial immune response and suggested that this route may have played a more important role than virus variability on the subsequent prognosis.