A significant proportion of patients with fulminant hepatic failure have clinical, biochemical and histological features suggestive of acute viral hepatitis, without serological evidence of either hepatitis A or B. The contribution of hepatitis C to such cases of non-A non-B fulminant hepatic failure is presently uncertain while hepatitis E is well recognized as a cause of fulminant hepatic failure in endemic areas. Nested polymerase chain reaction for detection of both hepatitis C and E virus as well as two serological assays for anti-hepatitis C virus and anti-hepatitis E virus western blotting (both IgG and IgM) were performed on acute sera of 42 consecutive cases of non A, non B-fulminant hepatic failure and on convalescent sera of 17 of 20 patients who underwent orthotopic liver transplantation. Fresh liver tissue, obtained at the time of transplantation, was also studied by polymerase chain reaction in eight cases. Evidence of an acute hepatitis E virus infection (hepatitis E virus RNA amplified from serum by polymerase chain reaction or serum IgM positive to western blot) was found in eight patients. One patient had anti-HCV at presentation but assays on later sera proved negative. Convalescent sera and sera obtained after orthotopic liver transplantation were all negative to both anti-HCV assay systems, but HCV RNA was not found in either serum or liver tissue in any case.(ABSTRACT TRUNCATED AT 250 WORDS)