Human papillomaviruses (HPVs), particularly types 16, 18, and 33, have recently been suggested as etiological agents for cervical neoplasia. However, few studies have explored this relationship among low-income minority women. This case-control study of cervical intraepithelial neoplasia (CIN), detected by Pap smear screening among South Carolina women, investigates the association between HPV positivity and the cytological continuum of CIN. Cervical spatulas and cytobrushes used to collect Pap smears from all women attending health department family planning clinics in three coastal South Carolina counties were saved for subsequent HPV detection and typing. Among this cohort of approximately 6000 cervical samples collected from March through December 1991, those with CIN, atypia, and other cervical abnormalities and women with normal cervical cytology were identified. Women with CIN II or III (n = 28) were 21.9 times more likely to be HPV 16, 18, or 33 positive, while women with CIN I (n = 114) were 11.7 times more likely to be HPV 16/18/33 positive when compared with women having normal cervical cytology (n = 223) and adjusting for potential confounders. Women with atypia (n = 115) were 3.0 times more likely to be HPV 16/18/33 positive. A chi 2 test for trend in increasing HPV 16/18/33 prevalence with increasing severity of cervical lesions was highly significant (P = 0.0001). HPV 6 and 11 were not associated with CIN, nor was there a significant trend of increasing prevalence with increasing severity of cervical lesions. Worthy of further research is our finding that the overall prevalence of HPV positivity was low in this relatively high-risk population of low-income, primarily black women.