Objective: To determine the seroprevalence of and risk factors for human papillomavirus (HPV) type 16 capsid antibodies in a large cohort of pregnant women. Methods: Antibodies against in vitro produced HPV-16 capsids were measured in stored sera from 2597 pregnant women enrolled from 1984 through 1989 in the Vaginal Infection and Prematurity Study, New Orleans site. Results: Women in this study were primarily black (83.4%) with a mean age of 23.4 years (standard deviation [SD], 5.1), mean number of sexual partners in lifetime was 3.3 (SD, 6.6), and the mean age at sexual debut was 16.7 years (SD, 2.2). Overall, 28.0% (n = 727) of these women were positive for HPV-16 capsid antibodies. In bivariate analysis, the presence of antibodies against HPV-16 was correlated with numerous demographic characteristics as well as history of various sexually transmitted diseases. However, neither current cervical or vaginal infection nor adverse obstetric outcome was associated with increased detection of HPV-16 antibodies. In multivariate logistic regression analysis, factors predictive of HPV-16 seropositivity were: more than five lifetime sexual partners (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.28, 2.52), 6 or more years of sexual activity (OR, 1.84; 95% CI, 1.22, 2.78), level of education (OR, 1.26; 95% CI, 1.03, 1.55), and history of Neisseria gonorrhoeae infection (OR, 1.53; 95% CI, 1.20, 1.96). Conclusion: HPV-16 seropositivity correlates with measures of sexual activity, confirming its role as a sexually transmitted disease, and its prevalence is similar to that in nonpregnant populations. HPV-16 seropositivity does not predict an adverse obstetric outcome.