To better characterize the natural history of disease due to human immunodeficiency virus (HIV) infection in African women. Prospective cohort study over a 2-year follow-up period. A total of 460 HIV-seropositive women and a comparison cohort of HIV-seronegative women recruited from prenatal and pediatric clinics in Kigali, Rwanda in 1988. Clinical signs and symptoms of HIV disease, AIDS, and mortality. Follow-up data at 2 years were available for 93% of women who were still alive. At enrollment, many seropositive women reported symptoms listed in the World Health Organization (WHO) clinical case definition of AIDS, but these were nonspecific and often improved over time. The 2-year mortality among HIV-infected women by Kaplan-Meier survival analysis was 7% (95% CI, 5% to 10%) overall, and 21% (CI, 8% to 34%) for the 40 women who fulfilled the WHO case definition of AIDS at entry. In comparison, the 2-year mortality in women not infected with HIV was only 0.3% (CI, 0% to 7%). Independent baseline predictors of mortality in seropositive women by Cox proportional hazards modeling were, in order of descending risk factor prevalence: a body mass index of 21 kg/m2 or less (relative hazard, 2.3; CI, 1.1 to 4.8), low income (relative hazard, 2.3; CI, 1.1 to 4.5), an erythrocyte sedimentation rate exceeding 60 mm/h (relative hazard, 4.9; CI, 2.2 to 10.9), chronic diarrhea (relative hazard, 2.6; CI, 1.1 to 5.7), a history of herpes zoster (relative hazard 5.3; CI, 2.5 to 11.4), and oral candida (relative hazard, 7.3; CI, 1.6 to 33.3). Human immunodeficiency virus disease was the cause of death in 38 of the 39 HIV-positive women who died, but only 25 met the WHO definition of AIDS before death. Human immunodeficiency virus disease now accounts for 90% of all deaths among child-bearing urban Rwandan women. Many symptomatic seropositive patients may show some clinical improvement and should not be denied routine medical care. Easily diagnosed signs and symptoms and inexpensive laboratory tests can be used in Africa to identify those patients with a particularly good or bad prognosis.