The association between certain human papillomaviruses (HPV) and cervical intraepithelial neoplasia (CIN) is well documented, but there is uncertainty about the strength of association and the role of co-factors is unclear. This population-based case-control study in Norwegian women 20-44 years of age included 103 cases with histologically confirmed CIN II-III and 234 age-matched and randomly selected controls. Cytological specimens from the cervix were analyzed using the polymerase chain reaction (PCR). In all, 91% of the cases and 15% of the controls were HPV DNA positive, giving a crude odds ratio (OR) of 67.2 (95% confidence interval: 28.6-157.5). The association between HPV 16 and CIN II-III was even stronger (crude OR = 123.9; 46.7 - 328.5). In logistic regression analysis, additional to HPV, only a high number of sexual partners and a low educational level contributed independently to the risk. The adjusted OR for the association between HPV and CIN II-III was 72.8 (95% CI: 27.6-191.9). The association between HPV and CIN remains very strong even after adjustment for proposed confounding factors. The results therefore support the role of HPV as a causative agent in the development of CIN.