A study was undertaken to investigate the role of hepatitis C virus (HCV) and hepatitis E virus (HEV), either alone or together, in the causation of sporadic acute viral hepatitis (AVH) and fulminant hepatitis (FH) by simultaneous detection of their genomes in serum samples using the reverse transcription and nested polymerase chain reaction (RT-PCR). A total of 50 patients were enrolled in the study of which 34 had AVH and 16 had sporadic FH. The serum samples were first tested for hepatitis B surface antigen (HBsAg) and immunoglobulin (Ig)M antibodies against hepatitis A virus (HAV), hepatitis B core antigen (HBcAg) and HEV and also antibodies against HCV using commercially available enzyme-linked immunosorbent assay (ELISA) kits. All samples were then subjected to RT-PCR using primers for both HCV and HEV simultaneously in the same reaction mixture. Hepatitis C or hepatitis E was diagnosed when either the antibodies or PCR or both were positive for the respective viruses. Evidence of hepatitis C was present in six of the 34 (17.6%) cases of AVH and two out of 16 (12.5%) cases of FH. Four patients in the AVH group and one of the fulminant hepatic failure (FHF) group were found to be positive by PCR and the rest by serology. But as a sole aetiological agent, HCV infection was found in only one (2.9%) case of AVH and in none of the FHF cases. Evidence of HEV infection was found in 22/34 (64.7%) and 8/16 (50%) cases of AVH and FHF, respectively. Excluding co-infection with other viruses, HEV was found to be the sole aetiological agent in 15/34 (44.1%) of AVH and 7/16 (43.7%) cases of FHF. In five (10%) (four AVH and one FHF) of the 50 cases, evidence of infection with both HCV and HEV was present. But only in two of these five cases, genomes of both HCV and HEV were co-amplified. In seven (four AVH and three FHF) out of 50 (14%) cases, no known viral agent could be detected. Our results suggest that HEV is the most common aetiological agent for both acute viral hepatitis and fulminant hepatic failure and that HCV is a rare cause of acute liver diseases although along with other viruses, evidence of either present or past HCV infection may be present in a substantial number of cases. Furthermore, advanced-stage pregnancy appears to be a potential risk factor for HEV infection and high rate of mortality in women. The study suggests that the method of simultaneous amplification of both HCV and HEV genomes could reduce the time, labour and cost involved in diagnostic work up of acute liver disease patients.