Intrafamilial transmission of hepatitis C virus (HCV) was studied in family members of 44 children with chronic hepatitis C infection (index cases). There were 22 males and the mean age of all patients was 9.5 years (range, 1.5 to 16 years). Eleven index patients were multitransfused because of thalassemia major. Aminotransferase serum concentrations and anti-HCV antibodies were evaluated in 77 parents (38 fathers) and 56 siblings (28 males; mean age, 11.2 years; range, 2.5 to 18 years). No sibling showed evidence of liver disease or HCV infection. Eight parents (14%) were found to be anti-HCV positive, but only one of them acquired HCV infection from an index case through an accidental needle stick injury. A nonsexual person-to-person transmission of HCV was conceivable only in a girl (index case) who had no risk factor other than the contact with anti-HCV-positive father. Vertical transmission played a role in five children (index cases) (three males) from five different mothers. Among the eight children belonging to these mothers, three did not show evidence of HCV infection although born after their HCV-infected siblings. Furthermore, we have not identified factors related to activity of disease or to duration of contact with index cases or to peculiar features of family members capable of favoring the spreading of HCV infection. Different from hepatitis b, pediatric age does not seem to represent a reservoir for HCV infection since the majority of children acquired HCV infection through parenteral routes and no HCV-infected child transmitted HCV infection horizontally.