Human hepatitis E virus (HEV) was first reported in 1980 and is now considered a major cause of acute non-A, non-B hepatitis in humans. HEV infection is reported throughout the world and occurs in epidemic form in developing countries where the disease is endemic and is often associated with water contamination after heavy rains or flooding. Sporadic human HEV infections occur in industrialized countries where infected individuals contract the infection while traveling to endemic regions. The fecal-oral route is considered the primary mode of HEV transmission in humans. HEV infection of pigs was discovered in 1997. Since 1997, sporadic HEV infections in industrialized countries have been reported in people who have not traveled abroad and are associated with HEV isolates genetically homologous to those found in domestic pigs. HEV infection of chickens and rats has since been documented in the U.S. and abroad.;Evidence suggests that pigs serve as an important reservoir for HEV and thus exposure to pigs, pork products, or pig organs may pose a risk of zoonotic or xenozoonotic infection. Swine HEV infection causes a subclinical, non-icteric hepatitis in growing pigs. Pigs experimentally-infected with swine HEV had no signs of clinical illness; however, they were viremic for 1 to 2 weeks, HEV was present in the liver of infected pigs, and the pigs shed a large amount of HEV in feces for several weeks. Similar results were demonstrated when pigs were infected with human HEV. We demonstrated that HEV infection of pregnant pigs does not induce reproductive failure. We also demonstrated that HEV could be transmitted by intravenous exposure of pigs to feces or liver collected from pigs in the early stages of infection. We subsequently demonstrated that a high dose and/or repeated exposure may be required for fecal-oral transmission of HEV and this is likely to be a common scenario in modern and traditional pig production facilities. HEV also can be detected in pig manure storage facilities such as concrete pits and earthen lagoons and we demonstrated that HEV found in the pit manure is viable and infectious to pigs. We attempted, but failed, to detect HEV in on-site drinking water or surface water on or near pig farms. These findings suggest a potential risk of contamination of water supplies by HEV in pig manure exists but evidence of this is lacking to date.;Cross-species infection with HEV among different species of animals has been demonstrated; swine HEV infects nonhuman primates, human HEV infects pigs, and chicken HEV infects turkeys. Swine and avian HEV have been shown to be genetically distant with nucleotide homology of approximately 60%. We demonstrated experimental infection of pigs with avian HEV. The avian HEV was found in the liver of inoculated pigs and was shed in feces for at least 3 weeks. Rat HEV failed to replicate in pigs. These findings further support the growing concern that pigs are an important reservoir of HEV and emphasize the critical role of pigs in the epidemiology of HEV.