"High-risk" types of genital human papillomavirus (HPV) infections are associated with anogenital cancer. As these cancers occur more frequently in immunosuppressed individuals, we sought to better characterize type-specific prevalence, clinical spectrum, and risk factors for anal HPV infection among homosexual men. Cross-sectional and follow-up study of 93 HIV-seropositive (HIV+) and 116 HIV-seronegative (HIV-) homo-sexual/bisexual men, with testing of anal swabs for HPV DNA by Virapap/Viratype assay. Overall, 57 (61%) HIV+ and 20 (17%) HIV- men had anal HPV detected (P < .0001). HPV types 16/18 were most common, accounting for more than 50% of infections. Among HIV+ men, HPV prevalence increased with declining CD4 cell count: 33% with counts of more than 750, 56% with counts of 200 to 750, and 86% with counts less than 200 (P = .01). HPV infection was also associated with younger age and increasing numbers of lifetime sexual partners for all men. Most infections were subclinical, with clinically apparent infection (anal warts) accounting for 35% of infections in HIV- men, 33% in asymptomatic HIV+ men, and 52% in men with AIDS/ARC. For both HIV- and HIV+ men, rates of anal HPV detection (23% and 60%) were greater than those for the perianal area (5% and 37%) or penile shaft (2% and 7%) (P < .001). Persistence of anal HPV for 6 months was more common among men with AIDS/ARC (95%) than among asymptomatic HIV+ men (62%) or HIV- men (61%) (P < .05). Anal HPV infections are common in homosexual/bisexual men and have a strong relationship to HIV-associated immunosuppression. Because most infections involve "high-risk" types of HPV, studies of their natural history are needed to clarify the risk of anal neoplasia in men with HIV infection.