Serologic and immunologic studies were performed in 38 African and 60 US patients with acquired immunodeficiency syndrome (AIDS), 100 African and 100 US heterosexual men and women, and 100 US homosexual men to examine the potential role of infectious agents in human immunodeficiency virus (HIV) infection. There were no significant differences in the prevalence of antibodies to cytomegalovirus, Epstein-Barr virus, hepatitis A and B viruses, herpes simplex virus, syphilis, and toxoplasmosis among the African and US patients with AIDS, African heterosexual controls, and US homosexual men. However, these four groups all demonstrated a significantly greater prevalence of antibodies to each of these infectious agents compared with US heterosexual men. Immunologic studies demonstrated a significant elevation of activated lymphocytes (HLA-DR and T3 positive) and immune complexes in both AIDS populations and African heterosexual and US homosexual populations, compared with the US heterosexual population. These data demonstrate that the immune systems of African heterosexuals, similar to those of US homosexual men, are in a chronically activated state associated with chronic viral and parasitic antigenic exposure, which may cause them to be particularly susceptible to HIV infection or disease progression.