The prevalence of hepatitis E virus (HEV) infections among 55 domestic swine living in the Kathmandu Valley of Nepal was investigated. Sera and stool specimens were collected from 47 free-roaming swine and examined for the presence of HEV genomic sequences by the reverse transcription-polymerase chain reaction. Sera from these animals, as well as sera from eight other swine, were also examined for the presence of HEV-specific antibodies by an enzyme-linked immunosorbent assay and by a fluorescent antibody blocking assay. Hepatitis E virus RNA was detected in the sera and/or stool of three of 47 swine, while HEV-specific antibodies were detected in 18 of 55 swine. These results indicate that HEV is a zoonotic virus, and that swine are among its natural hosts.