Genotype 4 hepatitis E virus (HEV) is the dominant cause of hepatitis E in the People's Republic of China; swine are the principal reservoir. Our study was conducted in 8 rural communities of southern China, where families keep pigs near their homes. Phylogenetic analysis showed that 23 of 24 concurrent virus isolates from this region are genotype 4 strains. Among the study populations, immunoglobulin G anti-HEV seroprevalence accumulated with age at approximately equal to 1% per year for persons < or =60 years of age. After age 30 years, seroprevalence increased at higher rates for male than for female study participants. The overall seroprevalence was 43% (range 25%-66%) among the communities. Infection rates were higher for participants between 25 and 29 years of age. The results suggest that HEV infection probably has been endemic in southern China for at least 60 years, with swine being the principal reservoir of human HEV infection in recent years.