Men with advanced human immunodeficiency virus (HIV) disease have a high prevalence of anal human papillomavirus (HPV) infection and potentially precancerous anal disease. To characterize prevalence of and risk factors for anal HPV infection and anal cytologic abnormalities, 37 HIV-positive and 28 HIV-negative participants in the San Francisco General Hospital Cohort Study were studied. A questionnaire was administered, followed by an anal examination consisting of two consecutive anal swabs for cytology and HPV DNA hybridization, and anoscopy with biopsy of visible lesions. Ten of 28 (36%) HIV-negative men and 19 of 37 (51%) HIV-positive men had anal HPV infection (p = 0.32). Risk factors for anal HPV infection included HIV positivity with a CD4 count < 200/mm3 (p = 0.03) and a history of smoking (p = 0.03). Abnormal anal cytology was found in 2 of 26 (8%) HIV-negative men and 10 of 36 (28%) HIV-positive men with cytology adequate for interpretation (p = 0.09). Risk factors for abnormal anal cytology included HIV positivity with a CD4 count < 200/mm3 (p = 0.006) and current smoking (p = 0.03). We conclude that the risk of development of anal disease and HPV infection was highest among HIV-positive men with a CD4 count of < 200/mm3, and that smoking may play a role in the pathogenesis of anal disease.