Human herpesvirus 6 (HHV-6), a member of the β-herpesvirinae subfamily, is highly seroprevalent, has a worldwide distribution, and infection usually occurs within the first two years of life. In this age group, HHV-6 causes febrile illness including exanthem subitum with seizures a recognised complication. The virus is predominantly T lymphotropic although it can infect a variety of cell types in vitro and CD46 has recently been identified as a cellular receptor. The virus persists in the host, with a latent state proposed in monocytes and bone marrow progenitor cells, and chronic infection in salivary glands. The virus is pathogenic in the post transplantation period and may be a cofactor in the progression of HIV disease. The virus has also been associated with multiple sclerosis (MS), with the virus detected in oligodendrocytes particularly in plaque regions. The role of HHV-6 in MS remains controversial and a more extensive understanding of its neurotropism and association with disease is required. Two variants of HHV-6 exist (A and B) and comparison of their complete nucleotide sequences shows the genomes to be colinear, with a high degree of homology. Variation in specific regions of the genome is more extensive and probably accounts for biological and pathological differences. Almost exclusively, variant B is associated with febrile illness in childhood and is the predominant variant detected in healthy individuals. The epidemiology of HHV-6A infection needs to be better defined, although it is significantly less prevalent. Biological, genetic, epidemiological and pathological findings suggest that the two variants are divergent. Copyright © 2000 John Wiley & Sons, Ltd.