OBJECTIVE To characterise risk factors for abnormal and cytology and anal human papilloma virus (HPV) infection in homosexual/bisexual men with advanced HIV related immunosuppression. METHODS Cross sectional study of men with Centers for Disease Control group IV HIV disease. METHODS The University of California San Francisco, AIDS Clinic. METHODS 129 homosexual or bisexual men with group IV HIV disease. METHODS A questionnaire was administered detailing tobacco, alcohol and recreational drug use, medical history, and sexual practices. Anal swabs for cytology and HPV studies were obtained, as was blood for CD4 levels. METHODS Abnormal anal cytology and anal HPV infection. RESULTS Abnormal anal cytology was detected in 39% of subjects and anal HPV infection in 93% as measured by polymerase chain reaction (PCR). Risk factors for abnormal cytology in multivariate analysis included HPV 16/18 infection (measured by PCR, RR = 2.1, 95% CI = 1.2-3.5) and intravenous drug use (RR = 1.8, 95% CI = 1.2-2.7). Infection with HPV 6/11 also had significantly elevated RRs in a separate model. Cigarette smoking, alcohol use, recreational drug use, and low CD4 level were associated with abnormal anal cytology in univariate analysis, as was infection with multiple HPV types and high levels of hybrid capture group B viral DNA. CONCLUSIONS Anal cytological abnormalities and HPV infection are common among homosexual/bisexual men with group IV HIV disease. In this study population, the main risk factors for abnormal cytology were HPV infection and intravenous drug use.