We have previously reported that among 200 women referred for colposcopy with smears suggesting mild dyskaryosis, medium or high copy numbers of human papillomavirus type 16 (HPV16) DNA identified patients with current high-grade cervical disease. We have followed up 95 women from that group who had histologically proven mild-grade cervical disease (cervical intraepithelial neoplasia grade 1, n = 37) or wart virus infection (n = 12) or who had no evidence of cervical abnormality at study entry (n = 43). Kaplan-Meier survival analysis of the 70 months' follow-up was used to identify baseline features that might affect the risk of progression. 3 women were lost to follow-up; data were available for the remaining 92. Among the whole group the probability of remaining free of high-grade cervical disease was 0.71. Women with a histological diagnosis of minor-grade disease were more likely to progress to high-grade disease than those with no evidence of abnormality (proportion disease-free 0.52 vs 0.90, p = 0.004). Stratification of the group according to median age (28 years) revealed a weak association between age and disease progression (p = 0.04). There was no difference in disease-free probability between HPV16-positive and HPV16-negative women (0.75 vs 0.65, p = 0.19). Nor was there a significant difference in disease-free probability when the group was stratified by HPV16 viral burden. These data show that a histological diagnosis of minor-grade cervical disease is a better long-term predictor of disease progression than is HPV16 positivity, irrespective of copy number. These findings do not support the simple view that HPV16 alone is the cause of high-grade cervical disease, including cancer.