Adults with chronic hepatitis C develop cirrhosis over a period of 6 to 20 years, but there are few reports of this disorder in children. To determine the histologic activity of chronic hepatitis C in children, we examined 31 biopsy specimens from 25 children (age range 3-16 years) with this disease. All patients were seropositive for antibody to hepatitis C virus by second-generation testing, and for HCV-RNA by the polymerase chain reaction. All cases were transfusion-associated. Patients were divided into two groups according to underlying disease: malignant disease or aplastic anemia (Group A, 17 cases) and non-malignant disease (Group B, eight cases). All patients in Group A, but only one in Group B, had received multiple transfusions. All patients in Group A had received intensive courses of cytotoxic and immunosuppressive agents. The histologic diagnosis was made using the standard criteria and Knodell's histology activity index. Chronic persistent hepatitis was more common in Group B (six patients) than in Group A (three patients). Chronic aggressive hepatitis 2B was found only in Group A (five patients). The mean histology activity index score was higher in Group A than in Group B (8.5 vs. 5.7). Six patients (four in Group A and two in group B) subsequently had a liver biopsy. The pathological diagnosis did not change after the second biopsy in any patient in Group B, while two patients in Group A showed a rapid progression of hepatitis. In each category of the histology activity index, periportal necrosis and intralobular necrosis were more severe in Group A than in Group B.(ABSTRACT TRUNCATED AT 250 WORDS)