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Background: Hepatitis E virus (HEV) is the major etiologic agent of enterically transmitted viral hepatitis in much of the developing world. Evidence provided in recent years shows that HEV is also prevalent in very low numbers in non-endemic countries. Recently, a cluster of three patients with acute hepatitis E but no history of travel to endemic countries was discovered in the geographical area provided with service by the Public Health Laboratory Groningen and Drenthe, The Netherlands.Objective: This lead to the question whether hepatitis E is a cause of unexplained hepatitis in this district.Study design: The prevalence of anti-HEV IgG and IgM among 209 patients with clinical signs of hepatitis, negative test for hepatitis A-C, no history of foreign travel and no other cause of hepatocellular damage was compared with a matched control group of 209 individuals.Results: We found a significant difference in seroprevalence between the two groups for IgG anti-HEV as determined with the Abbot HEV ETA (6.2% versus 0.5%); however this difference could not be confirmed with the Genelabs Diagnostics HEV IgG ELISA (6.7% versus 3.8%). For confirmed cases of IgM anti-HEV we also detected a significant difference between the two groups (3.3% versus 0.5%). Remarkably, the combination of IgG and IgM anti-HEV was only found among hepatitis patients.Conclusion: This study provides evidence of locally acquired hepatitis E in The Netherlands. Therefore, in cases of unexplained acute hepatitis. the diagnosis of hepatitis E should be considered even in the absence of foreign travel. (C) 2004 Elsevier B.V. All rights reserved.