Ninety-seven male homosexuals with the acquired immunodeficiency syndrome or other group IV human immunodeficiency virus disease were studied for anal human papillomavirus infection and intra-anal cytological abnormalities. Human papillomavirus DNA was detected in 52 subjects (54%), and 38 subjects (39%) were found to have abnormal anal cytological findings; anal intraepithelial neoplasia was detected in 15 specimens (15%). Abnormalities on anal cytological smear were significantly associated with the presence of human papillomavirus DNA, with a risk ratio of 4.6. Infection with multiple human papillomavirus types was common (12%) and was associated with a risk ratio for cytological abnormalities of 39.0. Median T4 counts of subjects with abnormal cytological findings were significantly lower than those with normal findings. These studies indicate that immunosuppressed male homosexuals have a high prevalence of anal human papillomavirus infection and anal intraepithelial neoplasia, and this population may be at significant risk for the development of anal cancer.