U.S. strains of swine and human hepatitis E viruses (HEV) are closely related genetically. We found that swine and human HEV differ in virulence and both induce subclinical, but morphologically discernable, hepatitis in experimentally infected SPF pigs. Experimental inoculation of pigs with human HEV may provide a useful model to study the pathogenesis of hepatitis E virus infection and test efficacy of human HEV vaccines.