To determine the natural course of cervical human papillomavirus infection, we prospectively studied all new patients referred to the colposcopy clinic at the Naval Hospital Bethesda, from April 1981 to August 1983, whose screening cervical cytology demonstrated features consistent with human papillomavirus infection as the only abnormality. Histologic confirmation of human papillomavirus infection was required for entry into the study. All patients were evaluated by repeat cytology, colposcopy, endocervical curettage, and colposcopically directed biopsy as indicated at intervals of three to six months. Patients who developed classic features of cervical intraepithelial neoplasia were treated by standard modalities, whereas patients with evidence of human papillomavirus infection without associated cervical intraepithelial neoplasia were not treated. Confirmation of the resolution of human papillomavirus infection required negative cytology and colposcopy on two consecutive evaluations. Of the 45 patients for whom complete follow-up data are available, five (11.1%) had cervical intraepithelial neoplasia at the time of their initial evaluation, 15 (33.3%) progressed to cervical intraepithelial neoplasia over an average of 10.9 months, 18 (40%) resolved over an average of 13.7 months, and seven (15.6%) persisted with neither progression nor resolution for an average of 21 months. These data suggest that about one-third of patients who have histologically confirmed human papillomavirus cervical infection can be expected to develop cervical intraepithelial neoplasia within a year.