The mechanism underlying the development of chronic infection with hepatitis B virus is not known. We have done two independent studies in Qatar, where such infection is common, to determine whether immunity to this virus is influenced by the HLA phenotype of an individual. The first study generated a hypothesis to test in the second. In both studies, there was a significant deficiency of HLA-DR2 and an excess of HLA-DR7 in patients with chronic persistent infection with hepatitis B virus. We conclude that HLA phenotype is one of the factors influencing the response to infection with this virus.