In a prospective study of 33 infants born to hepatitis C virus (HCV)-positive human immunodeficiency virus-negative mothers the vertical transmission of HCV occurred in 6.8%. The evolution of HCV infection in two babies was studied from birth up to 5 or 6 years of age, and the sequencing of the hypervariable region (HVR) of the putative envelope-encoding E2 region of the HCV genome was performed. The HVR1 sequence variability and the different serological profiles during follow-up could reflect the differences in HCV transmission routes, HCV genotypes, and clinical evolution of infection.While the estimated rate of vertical transmission of hepatitis B virus from Hbe antigen-positive mothers is nearly 100% in the absence of immunoprophylactic measures, the rate of hepatitis C virus (HCV) vertical transmission is still very widely debated in the literature (estimates range from 0 to 100%), and to date no specific study has investigated differences among prenatal, perinatal, and postnatal infections (12, 13). Many studies have confirmed that the risk of transmission may be enhanced by coinfection with the human immunodeficiency virus (HIV) (10,15,17).The follow-up of infection in newborns may elucidate some aspects of virus evolution; the HCV variant detected at birth may be considered the starting viral sequence for a particular host, allowing a more reliable analysis of sequence variability over time.This study evaluates the rate of HCV transmission from HCV RNA-positive anti-human immunodeficiency virus (HIV) antibody-negative mothers to their offspring and the clinical evolution of acquired infection. We carried out a longitudinal study of 33 anti-HCV-positive infants for 24 months, and two infected children belonging to this cohort were followed up until 5 or 6 years of age by evaluating several clinical and virological parameters and sequencing hypervariable regions (HVR) of the putative envelope-encoding E2 region of the HCV genome (5,7,8).Longitudinal study. In our study 2,263 anti-HIV antibodynegative pregnant women were screened for anti-HCV antibodies between June 1992 and June 1995; anti-HCV antibody positivity was found in 56 cases (2.4%), and 33 women were enrolled in a prospective longitudinal study of HCV transmission. Their ages ranged between 19 and 42 years (mean age, 28 years); 20 women (60%) had an acknowledged history of intravenous drug use, 1 (3%) was a health care worker with professional exposure (3%), 4 (12%) had an acknowledged history of anti-HCV antibody-positive sexual partners, and 8 (24%) had no risk factor. No woman was in interferon therapy. Only 2 pregnant women were diagnosed as chronic hepatitis sufferers based on histological findings by liver biopsy, and 26 were asymptomatic. Four women breast fed up to 10 to 12 months, and two breast fed up to 30 days. All but 3 of 33 babies were delivered vaginally.Serum samples were stored at Ϫ80°C within 3 h of collection in a day hospital. Testing for anti-HCV antibodies was done by a commercially available third-generation enzyme immuno...