To evaluate whether uncircumcised status is correlated with acquisition of human immunodeficiency virus (HIV), 502 homosexual men were surveyed; 85% were circumcised. HIV infection was significantly associated with uncircumcised status (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.2, 3.8), nonwhite race, intravenous drug use, sexual contact with an intravenous drug user, number of male partners, frequency of unprotected receptive anal intercourse, and with history of genital herpes, anal herpes, or syphilis. Uncircumcised status was significantly associated with older age, nonwhite race, and history of syphilis; it was inversely associated with intravenous drug use. Using logistic regression analysis, the adjusted OR for the association between HIV infection and uncircumcised status was 2.0 (95% CI, 1.0, 4.0). Uncircumcised homosexual men had 2-fold increased risk of HIV infection. The role of circumcision as an intervention strategy to reduce sexual transmission of HIV warrants consideration.