Epidemiological studies have demonstrated that cervical HPV infection and precancerous lesions of the cervix are more common in HIV-seropositive patients. However little is known about the natural history of these lesions in this population. In the present study cervical smears from 36 patients, 18 HIV-seropositive women and 18 matched controls were evaluated with the aim of quantifying morphological alterations and to evaluate DNA ploidy and HPV subtypes. Cervical lesions in HIV-seropositive patients were diploid in 50% of the cases compared to 25% in controls. The only HPVs identified by ISH were types 16/18 and no significant differences were observed in the control population. In contrast, cytological evidence of HPV infection and dysplastic changes was greatly increased in smears from HIV patients compared to HIV-seronegative women. Less than 5% of the cells showed HPV associated changes in controls while 10% to 30% of the cells were affected in HIV-patients. We suggest that the Papanicolaou test should be effective for detecting cervical disease and for a close follow-up of this population. Moreover, while additional studies with larger population groups and different population bases are needed, these findings are suggestive of the possible use of morphological criteria for the identification of HIV-seropositive subjects.