Acute and chronic liver dysfunction is common after allogeneic bone marrow transplantation (BMT). Although toxicity, graft versus-host disease (GVHD), and viral infections are the major causes, etiologic diagnosis is difficult and often remains unknown. We conducted a prospective study to establish the role of the infection with both the hepatitis C virus (HCV) and the recently discovered hepatitis G virus (HGV) in liver dysfunction after BMT. From January 1994 to December 1995, 59 patients who had undergone an allogeneic BMT at our institution were enrolled in the study. HGV-RNA was identified in serum by nested polymerase chain reaction (PCR), and HCV was studied by the presence of second generation enzyme-linked immunosorbent assay (ELISA)-antibodies and HCV-RNA by nested PCR. HGV-RNA was detected in 25 patients (42%) (before BMT in 18 and after BMT in 7). HCV-RNA was present in 12 patients (20%) (before BMT in 11 and after BMT in one). The presence of HCV-RNA and HGV-RNA was clearly associated with a previous history of blood transfusions. No significant association was found between viral infection and acute liver toxicity. Some degree of liver dysfunction was present 6 months after BMT in 25 of 40 evaluable patients (62%). Long-term liver dysfunction was more common among patients infected with HCV alone (3 of 4) or with both HCV and HGV (3 of 3) than in those infected with either HGV alone (eight of 13) or with no virus infection (10 of 20). We found a high prevalence of HGV infection in our BMT population. However, no role for HGV in liver disease could be established in this study, and the relationship between HGV infection and liver dysfunction requires further clarification.