In HIV-infected men, human papillomavirus (HPV) infection is strongly linked with the development of anogenital lesions but is not a sufficient factor to explain the neoplastic transformation of such lesions. We investigated the association between HPV and herpesvirus infections in penile and anal lesions from 54 HIV-seronegative and 54 HIV-seropositive men by means of colposcopy, histopathology and in situ hybridization. Our patients showed condyloma acuminata (39%), papular warts (35%) and macular warts (26%). High-grade lesions were predominant in the HIV+ men, whereas low-grade lesions were more frequent in the HIV- men. In the HIV+ group, potential oncogenic HPV were the most frequently detected (83.4%) whereas the "low-risk" HPV were found chiefly in HIV- men (62.1%). The CD4 number was lower in patients showing "high-risk" HPV than in men showing lesions without HPV or with non-oncogenic HPV. HPV types 6/11 were found mainly associated with koilocytosis or with AIN(PIN)I. Oncogenic HPV were more often detected in AIN(PIN)II-III. The herpesviruses DNA detection revealed a higher prevalence of HSVI and -2 than CMV and EBV in the studied biopsies. The frequency of HSV and CMV detection was higher in the HIV+ than in the HIV- men. A link was found between the "high-risk" HPV and the CMV detection whatever the population considered. The detection in HPV lesions of other sexually transmitted viral agents could therefore represent an important means of preventing progression of the anogenital disease, especially in immunosuppressed patients.