Previous reports indicate that swine can be experimentally infected with Asian isolates of human hepatitis E virus (HEV), which supports epidemiological data indicating that domestic swine can serve as a reservoir for the virus in parts of Asia and as such have the potential to transmit the virus to humans by the fecal-oral route or through contact with pork products. The increasing incidence of human HEV infections in the western hemisphere raises the question of whether or not pigs can play a role in the transmission of this virus in the Americas. Accordingly the susceptibility of swine to a New World isolate of the human hepatitis E virus, Mexico 14, was evaluated. No evidence of infection was detected in experimental pigs. However a high herd and individual prevalence rate for seroreactivity to recombinant HEV antigen was detected in Iowa swine during the selection of experimental pigs. These observations suggests that swine vary in their susceptibility to human HEV isolates. Whether or not swine are susceptible to other New World isolates of HEV and can serve as a reservoir for human infection remains to be determined. The significance of the high rate of seroreactivity of swine to recombinant antigen with respect to human and swine health is not known. An epidemiological study currently in progress should help answer this important question.