Understanding the natural history of human immunodeficiency virus type 1 (HIV-1) and opportunistic infections in sub-Saharan Africa is necessary to optimize strategies for the prophylaxis and treatment of opportunistic infections and to understand the likely impact of antiretroviral therapy. We undertook a systematic review of the literature on HIV-1 infection in sub-Saharan Africa to assess data from recent cohorts and selected cross-sectional studies to delineate rates of opportunistic infections, associated CD4 cell counts, and associated mortality. We searched the MEDLINE database and the Cochrane Database of Systematic Reviews and Cochrane Clinical Trials Register for English-language literature published from 1990 through April 2002. Tuberculosis, bacterial infections, and malaria were identified as the leading causes of HIV-related morbidity across sub-Saharan Africa. Of the few studies that reported CD4 cell counts, the range of cell counts at the time of diagnosis of opportunistic infections was wide. Policies regarding the type and timing of opportunistic infection prophylaxis may be region specific and urgently require further study.