A total of 87 HPV-positive patients with grade I and II cervical intraepithelial neoplasia (CIN I and II) were followed up by cytology and colposcopy every 3 months for more than 5 years following the first biopsy. These patients were classified into three groups (progressive, persistent, and regressive disease) according to the results. The human papillomavirus (HPV) genome and viral types were identified by Southern blot hybridization at Tm-40 degrees and Tm-20 degrees with DNA extracted from exfoliated cervical cells. The lesion progressed to CIN III in 4/87 patients (4.6%), persisted in 39 patients (44.8%), and regressed in 44 patients (50.6%). In the progressive disease group, HPV 16 was detected in 2 patients, HPV 33 in 1 patient, and HPV 52 in 1 patient. In the persistent disease group, HPV 58 was predominant (28%), whereas in the regressive disease group, there was no predominant HPV type. In 10/39 patients from the persistent disease group, cytological examination transiently revealed severe dysplasia and/or findings similar to carcinoma in situ. These patients showed severe cytological abnormalities only once or twice during the follow-up. These results suggest that the natural history of CIN possibly depends upon the type of HPV that infects the cervix, and the relative risk of progression was similar to that shown by previous cross-sectional studies.