This study was carried out to investigate the putative role played by the hepatitis E virus (HEV) in acute hepatic dysfunction in paediatric patients with acute non-A-C hepatitis. We also evaluated the diagnostic value for anti-HEV immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays relative to nested reverse transcriptase PCR (RT-PCR) for HEV RNA detection. Sixty-four children with acute hepatitis were included in the study, in addition to sixteen healthy children with matched age and sex. All studied subjects were negative for IgM antibody to hepatitis A virus, hepatitis B virus surface antigen, IgM antibody to hepatitis B virus core antigen, antibody to hepatitis C virus, and by RT-PCR for HCV RNA. HEV RNA was detected in 23.4% of patients, followed by detection of specific IgM in 17.2% and IgG in 12.5% of patients. Two cases were positive for IgG in the control group (12.5%). The sensitivity, specificity and accuracy were 26.7%, 85.7%, 71.9%, respectively, for IgM, and 26.7%, 91.8%, and 76.6%, respectively, for IgG. From this study we can conclude that HEV is a frequent virus found sporadically with acute hepatitis among paediatric patients. We cannot depend upon serology alone for diagnosis; rather, both molecular and serological methods must be applied for accurate diagnosis.