Acute hepatitis E (AHE) has rarely been reported in industrialized countries, but the rate of seroprevalence of hepatitis E virus (HEV) antibodies (anti-HEV) is inappropriately high. The sensitivity and specificity of the assay used to test for immunoglobulin G (IgG) and IgM anti-HEV have not been well established in areas where hepatitis E is not endemic (hereafter referred to as "nonendemic areas"). We collected serum samples from 13 AHE patients, 271 healthy subjects, and 160 other liver disease patients in Taiwan to test for HEV RNA by reverse transcription (RT)-PCR and for IgG and IgM anti-HEV by enzyme-linked immunosorbent assays. The sensitivities of IgG and IgM anti-HEV (relative to RT-PCR) were 86.7 and 53.3%, respectively. The specificities of IgG and IgM anti-HEV assays for diagnosing AHE were 92.1 and 98.6%, respectively. The rate of seroprevalence of IgG anti-HEV was 11% among healthy subjects in this nonendemic area, and it increased with age. In summary, IgG anti-HEV is a good diagnostic test for screening for AHE in nonendemic areas. The high rate of prevalence of anti-HEV in healthy subjects indicates that subclinical infection may exist.