OBJECTIVES: Our purpose was to define the prevalence of antibodies to hepatitis C virus among inner-city prenatal patients. We also sought to examine both the reliability of traditional hepatitis risk factors to predict evidence of infection among these women and the incidence of coinfection in this population with other blood-borne and sexually transmissible agents. STUDY DESIGN: An anonymous serosurvey was performed to define and compare anti-hepatitis C virus prevalences among women registering for prenatal care at both an inner-city, university hospital-based clinic and an academic private practice based at the same institution. RESULTS: Anti-hepatitis C virus antibodies were detected in 4.3% of 599 pregnant women screened. In comparison, 0.8% had positive antibody tests for human T-lymphotropic virus and 0.5% were positive for antibodies to human immunodeficiency virus. Evidence of chronic hepatitis B infection was seen in 0.8%. The relative risk of other coexisting infections was significantly higher among women with anti-hepatitis C virus antibodies than among those who were antibody negative. Substance abuse was the most commonly identified risk factor for anti-hepatitis C virus-positive status, although risk factor-targeted screening would have failed to detect half of the anti-hepatitis C virus-positive women in this study. CONCLUSIONS: Hepatitis C virus infection among inner-city pregnant women, with its potential for maternal-fetal transmission, represents a public health issue of sufficient magnitude to warrant more extensive study. More information is needed, given this documented reservoir of maternal seropositive, regarding the vertical transmissibility of the virus and the effects of coinfections on neonatal disease.