The prevalence and associated cytologic manifestations of cervical infection with human papillomavirus (HPV) types 6, 11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52, and 56 were studied among 500 consecutive women attending the Harborview Medical Center Sexually Transmitted Diseases (STD) Clinic in Seattle, WA. Using radiolabeled-probes without prior amplification of DNA, HPV DNA was detected in cervical specimens from 120 (24%) of the women and was found to be more prevalent than Chlamydia trachomatis (13%), Neisseria gonorrhoeae (12%), or mucopurulent cervicitis (20%). High-risk HPV types 16 or 18 were present alone in 5% of the women; intermediate-risk types 31, 33, 35, 45, 51, 52, or 56 in 3%; and low-risk types 6, 11, 42, 43, and 44 in 5%. In an additional 8% HPV DNA was detected but could be characterized only as being type 6, 11, 16, 18, 31, 33, or 35. Each grouping of HPV types was equally associated with squamous intraepithelial lesions (SILs) of the cervix. In the absence of SIL and koilocytosis, the cytologic changes associated with HPV infection included frequent binucleation and variation in nuclear size and chromatin distribution. Parakeratosis and hyperkeratosis without nuclear atypia were not associated with HPV DNA. The natural history and clinical significance of these HPV-associated lesions remain to be defined.