We have conducted a long-term prospective study of children undergoing bone marrow transplantation (BMT) to assess morbidity and mortality for liver disease. One hundred eleven consecutive children were enrolled between June 1985 and June 1995 and were followed-up for a median of 5.5 years after BMT. Before transplant 48/111 children (43%) had abnormal alanine aminotransferase (ALT), none were HBsAg+ and 4/111 were anti-HCV+. After BMT 4/111 patients (3. 6%) died of liver failure. No relationship was found between pretransplant hepatitis B (HBV) or C (HCV) infection or elevated transaminases and development of severe liver damage. Eighty-two out of one hundred and eleven patients (74%) had abnormalities of ALT after BMT, transient (n = 54) or persistent (n = 28). None developed clinical signs or symptoms of end stage liver disease or of cirrhosis during follow-up. No significant difference in prevalence of liver disease, was found between children with normal or abnormal ALT at BMT (relative risk [RR] = 1.04). HCV infection could be implicated in the etiology of chronic liver disease in 14/28 patients; 2 other patients were found infected by HBV alone (1 case) or combined with HCV (1 case). In the remaining 12 the etiology of chronic liver disease could not be defined. Posttransplant hepatitis B occurred in 4/111 children (3.6%), including a recipient from a donor who had been previously vaccinated against HBV, while no patient who had been vaccinated developed hepatitis B. The rate of posttransplant seroconversion to anti-HCV was 15%.