INTRODUCTION: In developed countries autochthonous hepatitis E infection is caused by hepatitis E virus (HEV) genotype 3 or 4 and mainly affects middle aged/elderly men. Host factors might explain why older men develop clinically overt disease. METHODS: Retrospective review of 53 patients with symptomatic autochthonous hepatitis E infection to determine putative host risk factors. Patients were compared with 564 controls with adjustment for age and sex. Anti-HEV seroprevalence was determined in controls and 189 patients with chronic liver disease. RESULTS: Mean age of the patients was 62.4 years, 73.6% were men. Compared with controls, patients with hepatitis E were more likely to drink at least 22 U alcohol/week (OR=9.4; 95% confidence interval=3.8-25.0; P<0.001). The seroprevalence of anti-HEV IgG in controls increased with age (P<0.001) but was similar in men and women. There was no association between alcohol consumption and anti-HEV IgG seroprevalence in the control group. There was no difference in the anti-HEV IgG seroprevalence between the controls and patients with chronic liver disease of all aetiologies, but seroprevalence was higher in controls (13.8%) than patients with alcoholic liver disease (4.8%, P=0.04). CONCLUSION: Clinically apparent hepatitis E infection is more common in individuals who consume at least 22 U alcohol/week. Patients with established chronic alcoholic liver disease have a low seroprevalence compared with controls. The reason for this observation is uncertain, but patients with alcoholic liver disease have clinically severe disease with a high mortality when exposed to HEV. The low seroprevalence in this group may represent a 'culled' population.