A newly developed assay for antibody to hepatitis E virus (anti-HEV) was used to study the rate of exposure to HEV infection in two Saudi areas: Riyadh (Central Province-788 people) and Gizan (Southern Province-630 people). These two regions were chosen for the study because the Riyadh area is an urban area and Gizan is considered rural, based on sewage disposal and water sanitation systems in each area. In both areas, HEV is endemic and acquisition of infection to the virus starts early in life and increases with age. In both areas, males are also at higher risk of acquiring the infection than females and this is probably because of social habits rather than genetic factors. The observation of higher anti-HEV prevalence in Gizan (14.9%) than in Riyadh (8.4%) (P < 0.0002) confirms earlier observations that the level of exposure to HEV is related to the hygienic conditions in the community and that improvement in sanitation is an effective measure in lowering the spread of infection.