Non-travel-related hepatitis E virus (HEV) genotype 3 infections in persons in the Netherlands may have a zoonotic, foodborne, or water-borne origin. Possible reservoirs for HEV transmission by water, food, and animals were studied. HEV genotype 3/open reading frame 2 sequences were detected in 53% of pig farms, 4% of wild boar feces, and 17% of surface water samples. HEV sequences grouped within 4 genotype 3 clusters, of which 1 is so far unique to the Netherlands. The 2 largest clusters contained 35% and 43% of the animal and environmental sequences and 75% and 6%, respectively, of human HEV sequences obtained from a study on Dutch hepatitis E patients. This fi nding suggests that infection risk may be also dependent on transmission routes other than the ones currently studied. Besides the route of exposure, virus characteristics may be an important determinant for HEV disease in humans.H epatitis E virus (HEV) is an RNA virus that causes liver infl ammation in humans, predominantly in developing countries. In the 1990s, serologic studies among blood donors in industrialized countries showed that anti-HEV seropositivity also occurred among a small percentage (1.1%-1.4%) of persons without a travel history to a hepatitis E-endemic region (1,2). Later studies confi rmed sporadic hepatitis E cases contracted in Europe, the United States, and other industrialized regions (3). HEV strains detected in mammals can be classifi ed into 4 major genotypes that are represented by Burmese isolates (genotype 1), Mexican isolates (genotype 2), US isolates (genotype 3), and recent Chinese isolates (genotype 4) (3). In addition, virulent and avirulent HEV strains that infect birds have recently been identifi ed (4,5). In industrialized countries, non-travel-related HEV infections are caused by genotype 3 (Europe, United States, Japan, New Zealand, Argentina) and genotype 4 (Japan, People's Republic of China).A possible role for zoonotic transmission in the epidemiology of human HEV episodes has been suggested after viral RNA was detected in different animal species, and these viruses were found to be closely related to HEV strains found in humans. The fi rst animal in which HEV genotype 3 was identifi ed and characterized was pig in the United States (6). HEV strains of genotypes 3 and 4 have since been detected in pigs in many other countries, and these strains were found to be genetically closely related to HEV strains originating from humans in the same geographic region (7,8). Serologic studies have also indicated a broad host range of HEV. In many animal species such as cows, cats, dogs, rodents, and mongooses, immunoglobulin G to HEV was detected by using several serologic tests. However, HEV RNA was not detected in these animals and because of the lack of positive reference materials to evaluate these tests, the results must be interpreted with caution (9-12).Assuming a zoonotic source for HEV infections, exposure to reservoirs of HEV might occur through contact with infected animals and animal products. Consumption of ...