Hepatitis E virus (HEV) is one of the major causative agents of acute hepatitis in many developing countries. Recent intensive examination has revealed the existence of non-imported cases in industrialized countries. The patient was a 25-year-old Japanese female with acute hepatitis. Laboratory test demonstrated positive anti-nuclear antibody (ANA), anti-smooth muscle antibody (ASMA) and high level of serum immunoglobulin G (IgG). The patient was negative for serum markers of hepatitis A, B or C virus infection. She demonstrated a clinical course similar to severe autoimmune hepatitis, including response to prednisolone therapy. After a few years, with the availability of tests for the serum antibodies to HEV, we examined the frozen stocked sera of the patient and found her exact diagnosis was acute hepatitis E. Although we could not detect HEV-RNA, which is positive only in limited period of acute phase, serum IgA and IgG antibodies to HEV were positive and the titer of IgA and IgG antibodies were declined with the time course. In conclusion, we must take into consideration of HEV infection for the diagnosis of acute cryptogenic hepatitis including autoimmune hepatitis. Further studies are feasible to understand the pathogenesis of liver injuries induced by HEV infections.