The objectives of this study were to evaluate the frequency and determinants of rectal bleeding and the association between rectal bleeding and risk of human immunodeficiency virus (HIV) infection among homosexual/bisexual men in Mexico City. Men who requested anonymous HIV testing at a public clinic in Mexico City and who reported engaging in any homosexual behavior were eligible to participate in this study. Trained staff collected information on demographic factors, sexual behavior, psychological states, and HIV serostatus from all consenting, eligible clients. Logistic regression modeling was used to investigate the independent effect of risk factors among 2, 758 men who were tested between June 1991 and December 1992. Bleeding during anal intercourse was a common occurrence: More than one third of the men in the study reported some bleeding, and 8% reported bleeding in half or more of their intercourse episodes. The prevalence of HIV infection among bleeders was 42% as compared with 28% in nonbleeders (p < 0.0001), and the adjusted odds ratio was 1.8 (95% confidence interval (CI) 1.1–2.8) for men who bled in more than half of their anal intercourse episodes relative to nonbleeders. There was a trend of increasing HIV seroprevalence with increasing frequency of rectal bleeding (p = 0.001). Nine percent of all HIV infections and 42% of infections among frequent bleeders were attributable to rectal bleeding. Men who reported both rectal bleeding and anal warts were 3.5 (95% Cl 2.1–5.8) times more likely to be HIV-infected in multivariate analysis than men reporting neither rectal bleeding nor anal warts. Determinants of rectal bleeding included older age, more education, more receptive anal intercourse than insertive intercourse, receptive digital-anal contact, anal warts, and genital ulcers. Among men reporting sex with men in Mexico City, rectal bleeding is common. It is an independent risk factor for HIV infection, and warrants attention in acquired immunodeficiency syndrome prevention efforts. Rectal bleeding that results from rupture of anal warts may be an especially effective portal of HIV transmission. Am J Epidemiol 1996; 144: 817–27.