A total of 532 women with established cervical HPV infection have been prospectively followed (without treatment) since 1981 for a mean of 45 (SD 21) months. The patients were examined by colposcopy, PAP smears and/or punch biopsy every 6 months. The life-table method was applied to analyze the clinical course (i.e. regression and progression) of the HPV lesions, stratified by their colposcopic pattern, PAP smear findings and grade of CIN. During the follow-up, 107 (41.8%) of 256 patients with HPV-NCIN lesion in the first punch biopsy, experienced spontaneous regression. The corresponding proportions for HPV-CIN I, HPV-CIN II and HPV-CIN III lesions were 31.1%, 34.2%, and 20.7%, respectively. In the overall comparison between these four groups, the heterogeneity in the probability of regression was statistically significant (p = 0.0005). Clinical progression was also associated significantly with the histological grade of the lesions in the first biopsy. Progression rate was only 5.8% for HPV-NCIN lesions, as compared to 12.3% for HPV-CIN I, 20% for HPV-CIN II, and 55.2% for HPV-CIN III. The probability of progression varied significantly between the four groups (p less than 0.00001). Cumulative proportion of regression was 46% for patients with PAP smear class I, 84% with class II, and 82% for those with class III, cells, i.e. PAP smear was not of value in predicting the regression. However, PAP smears predicted clinical progression (p = 0.006 overall).(ABSTRACT TRUNCATED AT 250 WORDS)