Severe liver damage revealed by a sharp transaminase elevation may be seen in patients with leukemia. This may be due to several possible causes, including viral hepatitis, chemotherapy-induced hepatotoxicity and leukemic infiltration. HCV infection may be suspected to play a relevant role as these patients are often heavily transfused after the onset of their hematologic disorder. We have therefore examined the role of HCV in 15 children with leukemia who developed severe liver damage shortly after the diagnosis of leukemia. All patients were tested for HCV-RNA by the polymerase chain reaction at the time of peak SGPT elevation and for anti-HCV on serial serum samples taken thereafter. Only one patient (6.6%) showed hepatitis C viremia and none developed confirmed anti-HCV positivity during follow-up, suggesting that HCV had not played a major role in causing these severe episodes of liver necrosis. This is in agreement with observations made in non-immunocompromised patients in whom fulminant hepatitis is only exceptionally due to HCV.