The Italian Seroconversion Study (ISS) involves 16 major HIV-treatment centers across Italy and about 1,200 individuals. These individuals were HIV-negative less than 2 years before the first positive test and seroconverted between 1980 and 1994. The majority were infected through i.v. drug use (56%), male-to-male sex (25%), and heterosexual contact (7%). For each end point, crude and adjusted relative hazards were calculated using standard survival techniques such as Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression models. Autoregression models were used to describe CD4 cell reductions. Objectives were as follows: to estimate HIV disease progression rates; to assess whether there are differences in the rate of development of severe immunosuppression, AIDS, and death according to age, gender, and exposure category; to identify co-factors and predictors of disease progression; and to evaluate the clinic-based population “effect” of antiretroviral treatment. The risk for developing AIDS among individuals in the ISS cohort was less than 50% by 10 years after HIV seroconversion. Using univariate analysis, more rapid progression was found for older individuals than for younger individuals and for homosexual men compared with those in other exposure categories. No difference between men and women was observed. After adjusting for age, differences among exposure groups disappeared. Individuals with a history of acute HIV disease were more likely to develop AIDS than other seroconverters. Co-infection with HCV and HTLV-II did not accelerate progression to AIDS. The cumulative incidence of receiving pre-AIDS therapy within 7 years of seroconversion was 49.2% (95% CI 45.3-53.0). The relative hazards of developing AIDS in patients who started treatment with zidovudine (AZT) monotherapy was 0.57 (0.36-0.91) and 0.92 (0.64-1.33) within the first year and after 1 year from AZT initiation, respectively. The effect was greater among homosexual men than among i.v. drug users. In conclusion, incident cohort studies may provide accurate information on incubation time and co-factors for disease progression. Observational studies may also provide useful information about the effect of treatment at the community level, which may complement the results of clinical trials.