In this study we assessed the seroprevalence of hepatitis E virus (HEV) infection in both the Italian population and immigrants from developing countries in Foggia (Apulia, Southern Italy). The seroprevalence of HEV was determined in 1217 subjects [412 (34%) immigrants and 805 Italian subjects (blood donors, general population, HIV-positive, haemodialysis patients)]. Serum samples were tested for anti-HEV and confirmed by Western blot assay; in positive patients HEV RNA and genotype were also determined. There were 8·8% of patients that were positive to anti-HEV, confirmed by Western blot. The prevalence in immigrants was 19·7%, and in Italians 3·9% (blood donors 1·3%, general population 2·7%, HIV-positive patients 2·0%, haemodialysis patients 9·6%). Anti-HEV IgM was found in 38/107 (35·5%) of the anti-HEV-positive serum samples (34 immigrants, four Italians). This study indicates a higher circulation of HEV in immigrants and Italian haemodialysis patients, whereas a low prevalence of HEV antibodies was seen in the remaining Italian population.