In order to study the association between seropositivity against human papillomavirus-type-16 capsids and CIN II-III in the general population in ages at which high-grade cervical dysplasia arises, 90 cases and 216 controls participating in a population-based case-control study of incident CIN II-III, were analyzed for the presence of HPV antibodies, HPV DNA and for the influence of behavioral factors. A significantly higher proportion of cases than controls were seropositive. Of HPV-16-DNA-positive cases and controls, 42 and 14% respectively were seropositive. A similar proportion of seropositivity was found among the 172 cytologically normal, HPV-DNA-negative controls. However, seropositivity was closely linked to the sexual history of the women. Logistic-regression analyses, adjusting for sexual behavior, smoking history and educational level, revealed that CIN II-III was associated with HPV-16 seropositivity and with HPV DNA. Controlling for the presence of HPV DNA indicated that antibodies were not independently associated with CIN. The low correlation between the presence of HPV antibodies and DNA, the finding that the association between seropositivity and CIN depended on the presence of HPV DNA, and the association of seropositivity with sexual history, may be explained by serology detecting both past and present persistent infections and presence of HPV DNA, reflecting mostly transient infections in controls and persistent infections in cases.