Recent studies have documented a considerable degree of genetic divergence among wild-type hepatitis A virus (HAV) strains recovered from different geographical locations. Human HAV strains can be grouped into four genotypes (I, II, III and VII) and unique simian strains belong to three additional genotypes (IV, V and VI). Between each of these genotypes, the nucleotide sequence varies at 15-25% of base positions in the P1 region. Despite this, there is good evidence that most, if not all, human strains of HAV are closely related antigenically. In contrast, although simian strains recovered from Old World monkeys are cross-reactive in immunoassays employing polyclonal antibodies, these strains have significant antigenic differences from human HAV strains. Nonetheless, because biological differences in the host range of these strains apparently preclude significant human infection, this is unlikely to pose a problem in controlling HAV infections with active immunization. Inactivated and attenuated vaccines produced from genotype I human strains (HM175 or CR326) are likely to provide protection against all relevant human HAV strains.