OBJECTIVE Current recommendations for treatment of human immunodeficiency virus (HIV) infection and for prophylaxis against associated opportunistic infections in North America are largely based on observations of HIV infection in males. In an effort to determine whether the natural history and clinical course may be different, with implications relevant to prophylaxis against opportunistic infections, we have documented the clinical courses of the first 24 known cases of acquired immunodeficiency syndrome (AIDS) in women in Rhode Island, most of whom developed Centers for Disease Control-defined AIDS before the availability of an effective antiviral agent (i.e., zidovudine) or a well-defined approach to prophylaxis against opportunistic infections (e.g., oral trimethoprimsulfa). METHODS The subjects in this study are 24 women with AIDS who were treated by members of the Brown University medical faculty from June 1982 through June 1988. All patients had thorough clinical evaluations and appropriate laboratory studies as they became available. All were followed at intervals no greater than two months. All opportunistic infections were treated by appropriate, specific antimicrobial therapy. When zidovudine became available, it was administered to all remaining patients in the study. All subjects were counseled about HIV infection, its modes of transmission, and the early symptoms of opportunistic infections. RESULTS These observations yielded the following three major findings: (1) Candida esophagitis was the most common (38%) AIDS-defining event; (2) Pneumocystis carinii pneumonia was less frequently the AIDS-defining event (13%) and occurred less commonly during the illness (29%) than in North American males with AIDS; (3) Of 14 women in whom the diagnosis of AIDS was established before January 1, 1987, the mean survival time after diagnosis was greater than 20 months. CONCLUSIONS More information on the natural history of HIV infection in North American women is urgently needed. If more extensive data from other geographic regions confirm the observations in this study, the optimal approach to prophylaxis against opportunistic infections in women with AIDS may be substantially different from that which is most appropriate for males.