Hepatitis E virus (HEV) is the major agent of acute hepatitis in developing countries where the infection occurs sporadically or in large waterborne epidemics. HEV, classified in the Caliciviridae, is not culturable. The detection of HEV RNA by RT-PCR in serum and stool samples is reliable during the 7 to 15 days following the onset of the disease. Restriction endonuclease analysis, cloning and sequencing of PCR products allow a phylogenetic analysis of HEV isolates. Although they belong to a single serotype, strains recovered from different geographical regions display a significant genetic heterogeneity. Sequencing data from ORF1 and ORF2 regions has led to the characterization of 3 distinct genotypes: genotype I gathering the Asian and African subgenotypes; genotype II gathering swine and human US strains; genotype III limited to the Mexico prototype. Novel variants are currently described from Africa (Nigeria), China and Europe (Greece and Italy). Each genotype appears to be related to a well defined geographical area. Nevertheless, a genetic variability is observed within endemic regions such as Asia or Africa. Nigerian endemic isolates especially could represent an intermediate stage in the evolutionary process towards genetic diversity. The animal reservoir, proved by the detection of HEV sequences by PCR among pigs in Nepal and in the USA, could help to resolve unanswered questions about the origin of HEV genotypes, their spread and evolution.