Our objective was to describe associations among male circumcision, behavioral and demographic variables, ulcerative and nonulcerative sexually transmitted disease (STD), and human immunodeficiency virus (HIV) infection via a cross-sectional study in Kigali, the capital of Rwanda. Our subjects were 837 married men who volunteered for HIV testing and counselling. Uncircumcised men had a relatively low-risk profile in that they reported fewer lifetime sexual partners and prostitute contacts than circumcised men and were more likely to live in rural areas with lower HIV prevalence rates. Uncircumcised men were also less likely to report a history of sexually transmitted disease (64% versus 73%, p = 0.01), although they were more likely to report genital ulceration (GUD) (24% versus 17%, p < 0.03) and to have inguinal adenopathy noted on physical exam (42% versus 29%, p = 0.009). Despite the low-risk profile, uncircumcised men had a higher prevalence of HIV infection than circumcised men (29% versus 21% HIV positive, p = 0.02), which was most marked in men reporting five or more lifetime sex partners (36% versus 23% HIV positive, p = 0.005) or contact with prostitutes (35% versus 23% HIV positive, p = 0.009). Circumcision remained a predictor of HIV infection in multivariate analyses (multivariate odds ratio 1.69, 95% confidence interval 1.16-2.47). Lack of circumcision is associated with a higher risk of HIV infection in Rwandan men. Further research is needed to determine whether this higher risk is due in part to poor hygiene or to complex mechanisms operating through the acquisition of other sexually transmitted diseases. Circumcision may be an appropriate risk reduction approach for men with known exposures to the virus when there are constraints to alternatives, such as condom use.