Abstract. A study of antibody prevalence for hepatitis A virus (HAV) and hepatitis E virus (HEV) was carried out in southwestern Vietnam in an area adjacent to a known focus of epidemic HEV transmission. The purpose of this investigation was first to provide a prevalence measure of hepatitis infections, and second to determine the outbreak potential of HEV as a function of the susceptible population. Blood specimens collected from 646 persons in randomly selected village hamlets were examined by an ELISA for anti-HEV IgG and anti-HAV IgG. The prevalences of anti-HEV IgG and anti-HAV IgG were 9% and 97%, respectively. There was a significant increase (P Ͻ 0.01) in age-specific anti-HEV IgG. A notable increase in anti-HAV IgG prevalence (P Ͻ 0.0001) occurred between child populations 0-4 (64%) and 5-9 (95%) years of age. No evidence of familial clustering of anti-HEV IgG-positive individuals was detected, and household crowding was not associated with the spread of HEV. Boiling of water was found to be of protective value against HEV transmission. A relatively low prevalence of anti-HEV indicates considerable HEV outbreak potential, against a background of 1) poor, water-related hygiene/sanitation, 2) dependence on a (likely human/animal waste)-contaminated Mekong riverine system, and 3) periodic river flooding.Epidemic and sporadic hepatitis E virus (HEV) transmission has been documented throughout the developing world 1 (Balayan MS, unpublished data). In southeast Asia (in contrast to other geographic regions), HEV occurrence is generally reported as a rural rather than urban phenomenon.2 The proportion of (sporadic) acute hepatitis cases attributed to HEV reported in cities such as Jakarta (Indonesia) and Hanoi (Vietnam) has been found to be very low: 3% and Ͻ 1%, respectively 3 (Persahabatan Hospital, Jakarta, Indonesia, unpublished data). Conversely, foci of epidemic HEV transmission have been recognized in jungle/ riverine areas of Indonesian Borneo (Kalimantan) 4,5 and the Mekong River delta region of Vietnam.6 Transmission determinants associated with worldwide spread of enteric HEV are principally water-related. 4 In developing areas, the spread of hepatitis A virus (HAV) is also related to waterborne transmission, whereas in more developed settings, infections are predominately acquired through contact with an infected person, usually a child with inapparent infection, and occasionally from contaminated food or drink. Dependence on a single (contaminated) water source for drinking/hygiene/sanitary purposes has been implicated in both epidemic and sporadic (community-acquired) spread of HEV and HAV. Epidemic HEV infections were attributed to well water in Somalia 7 and river water in Indonesia 4,5 and Vietnam. 6 However, unlike HAV transmission, there is little evidence of person-to-person spread of HEV. Also, HEV infections, when compared with HAV, are characterized by 1) a longer incubation period, 2) case-fatalities in pregnant women (10-24%), and 3) poor protection by gamma globulin.7-9 An investigati...