The relationship between infection with different human papillomavirus types and cervical intraepithelial neoplasia was studied in a group of 398 women seen in a private gynecology practice in Washington, D.C. Each woman was assessed for human papillomavirus infection by Southern blot hybridization analysis of cervical cells obtained by swab. The human papillomavirus results were correlated with the results of Papanicolaou smears taken the same day and with data abstracted from medical records regarding past cervical disease. Subjects with normal cytologic findings at the time of human papillomavirus testing were followed up for an average of 2 to 3 years with additional Papanicolaou smears. At the time of human papillomavirus testing, 58% (19/33) of women with cervical intraepithelial neoplasia had detectable human papillomavirus deoxyribonucleic acid in contrast to 10% (28/289) of women with normal cytologic findings (p less than 0.001). This association persisted after statistical adjustment for age and current use of oral contraceptives, a factor that appeared to increase the detection of human papillomavirus. Among women with no current cytologic evidence of neoplasia, human papillomavirus detection was more likely in those with a history of past genital neoplasia (p = 0.05). In the follow-up study, 15% (3 of 20) of cytologically normal women who were human papillomavirus-positive at baseline subsequently exhibited cervical cells suggestive of cervical intraepithelial neoplasia compared with only 5% (9 of 195) of human papillomavirus-negative women. However, this difference reflected recurrent and not incident neoplasia.