Basal levels of the interferon-associated enzyme 2' ,5'-oligoadenylate synthetase were studied in lymphocytes of 46 patients with acute viral hepatitis and in 46 patients with chronic hepatitis B. Measurement of in vitro production of 2',5'-oligoadenylate synthetase following overnight incubation of lymphocytes with exogenous interferon was used to assess functional capacity of the lymphocyte interferon system. In acute hepatitis patients, an early but transient elevation of 2',5'-oligoadenylate synthetase was observed; the mean level at 1 week was significantly greater than the mean level at 4 weeks after the onset of their illness (p c 0.01). Serial 2',5'-oligoadenylate synthetase levels did not identify those patients who were to progress to chronic hepatitis. Patients with chronic hepatitis B infection, regardless of background liver histology, generally had normal basal lymphocyte 2',5'-oligoadenylate synthetase levels. In both acute viral hepatitis and chronic hepatitis B, there was an inverse correlation between basal 2',5'oligoadenylate synthetase level and 2',5'-oligoadenylate synthetase response to overnight incubation with interferon, a finding that suggested a transient downregulation of interferon responsiveness. These findings provided no support for the hypothesis that there is an inherent or persistently induced deficiency in the interferon system in acute or chronic hepatitis B.