Ninety per cent of patients infected in adult life with the hepatitis B virus clear the virus completely and 10% develop chronic infection. There is evidence for the involvement of interferon in the clearance of acute hepatitis B virus infection. We report that, in in vitro tests, some hepatitis B virus carriers have a reduced capacity to produce alpha- and gamma-interferon which is unrelated to the level of viral replication and to the severity of the liver disease and that the level of 2-5 oligoadenylate synthetase in their livers is only minimally elevated compared to controls. Treatment with lymphoblastoid (alpha-) interferon leads to a marked rise in 2-5 oligoadenylate synthetase activity. These data indicate that some patients with chronic hepatitis B virus infection acquired in adult life have a partial deficiency of production of alpha-interferon but can respond to exogenous alpha-interferon. These observations provide a logical basis for attempts to treat this condition with interferons.