In a study of human immunodeficiency virus type 1 (HIV-1)-uninfected African prostitutes, 83 (67%) of 124 sero converted to HIV-1. Oral contraceptive use (odds ratio [OR], 3.1; 95% confidence interval (CI], 1.1–8.6;P < .03), genital ulcers (mean annual episodes, 1.32 ± 0.55 in seroconverting women vs. 0.48 ± 0.21 in seronegative women; P < .02) and Chlamydia trachomatis infections (OR, 3.6;CI, 1.3–11.0; P < .02)were associated with increased risk of HIV-1 infection. Condom use reduced the risk of HIV-1 infection (OR, 0.11; CI, 0.05–0.27; P < .0001). Stepwise logistic regression analysis confirmed independent associations between HIV-l infection and oral contraceptive use, condom use, genital ulcers, and C. trachomatis. The presence of other sexually transmitted diseases may in part explain the heterosexual HIV-1 epidemic in Africa and may represent important targets for intervention to control HIV-1 infection.