BACKGROUND: Investigation of immunologic values in children vertically exposed to hepatitis C virus (HCV) infection could help explain the higher risk of infection in girls and indicate mechanisms of spontaneous viral clearance and possible long-term immunologic effects. METHODS: Prospective study of children born to HCV-infected women. Lymphocyte and neutrophil measurements were age-standardized using the LMS method (this summarizes the changing age distribution of a variable). Associations between maternal and infant characteristics and lymphocyte and neutrophil z-scores were quantified using linear regression allowing for repeated measures. RESULTS: HCV-infected children, girls, and those born to HCV/human immunodeficiency virus (HIV)-coinfected women had significantly higher lymphocyte z-scores than HCV-uninfected children, boys, and children born to HCV-only-infected women, respectively. Peak absolute lymphocytes were significantly lower for infected children with evidence of viral clearance than for persistently infected children. Girls also had significantly higher neutrophil z-scores than boys but HCV-infected children had significantly lower neutrophil z-scores than uninfected children. CONCLUSIONS: The gender associations are in line with those observed among children born to HIV-infected women, suggesting general gender-based differences in response to infection. Age-related standards for uninfected children could be used to assess immune function in other pediatric diseases and these results suggest that gender-specific reference values should be used at least for the first 2 years of life.