Serial serum samples obtained from 27 patients with fulminant hepatic failure (FHF) in a variety of etiology were tested for anti-hepatitis C virus antibody (anti-HCV). Seven out of 10 patients (70%) with FHF due to hepatitis B virus (HBV) infection were positive for anti-HCV, showing a significantly higher rate than that in acute HBV hepatitis (0/17, 0%): In particular, all 3 post-transfusion HBV-FHF cases were found to be positive for the antibody. The incidence of anti-HCV in sporadic non-A non-B (NANB)-FHF patients (7/11, 64%) tended to be greater than that in acute sporadic NANB hepatitis as recently surveyed in this country. In addition, anti-HCV was also detected in a patient with hepatitis A virus (HAV)-FHF and in 2 out of 4 drug-induced FHF patients. Moreover, anti-HCV appeared earlier in FHF (median; 27.5 days, n = 9) regardless of etiology, when compared to acute NANB hepatitis (3 to 6 months). Hence, co-infection and/or superinfection of HCV with enhanced antibody response may play an important role in the development of this fatal disease.