Homosexual men are at high risk of anorectal human papillomavirus (HPV) infection, HPV-related anal cancer, and precancer, conditions known to increase with immunosuppression. The relationship between anal HPV infection, human immunodeficiency virus (HIV) infection, and immunosuppression was studied in homosexual men seen at a sexually transmitted disease clinic. History or presence of warts on rectal examination, and detection of anorectal HPV DNA were each significantly associated with HIV seropositivity after adjusting for age, previous sexual behavior, and cultural or serologic evidence of other sexually transmitted diseases, including those previously identified as risk factors for acquisition of HIV infection. Decreased mean levels of T4 lymphocytes were significantly associated with the detection of anal HPV DNA. Prospective studies are needed to determine incidences of anal HPV infection and cancer among HIV-seropositive and -seronegative mean and to determine the temporal relationship of these infections to one another.