The aim of this study was to assess the rate of clinical progression to early and late stages of human immunodeficiency virus-2 (HIV-2) infection. CD4 cell counts and other potential prognostic markers for disease progression were also evaluated. In January 1990 an open prospective cohort of police officers in Guinea-Bissau was initiated with yearly serological and clinical follow-up. Follow-up ended in June 1998. Symptoms were classified according to the World Health Organization staging system. The analysis included 148 HIV-2-seropositive subjects and 177 HIV-seronegative controls. 25 of the HIV-2-positive individuals were seroconverters (seroincident cases). The progression rate to stage 3 of HIV-2-positive subjects in stage 1+2 was 8.6/100 person-years (py) (rate ratio 6.2 compared with HIV-negative controls, 95% confidence interval 2.7-14.2, p < 0.001), and the progression rate to stage 4, i.e. acquired immunodeficiency syndrome (AIDS), was 2.1/100 py. HIV-2-positive people in stage 3 at inclusion progressed to AIDS at a rate of 16.9/100 py. CD4% < or = 20 was found to be a significant prognostic marker for progression to stage 4, both from stage 1+2 and from stage 3. The clinical progression in this cohort of HIV-2-infected subjects was generally lower than that in HIV-1-positive cohorts.