We studied the natural course of high-risk human papillomavirus (HPV) infection and cytological regression in women referred for colposcopy because of abnormal cervical smears. We found that high-risk HPV clearance preceded regression of cervical lesions by an average of 3 months. The cumulative 1-year rate of cytological regression was similar in women with mild and moderate dyskaryotic cervical smears. Thus, retesting of high-risk HPV after 6 months in women with mild to moderate dyskaryosis predicts cytological regression.