The production in vitro of interferon alpha and gamma by peripheral blood mononuclear cells of 25 patients with chronic hepatitis B and 13 patients with chronic hepatitis non-A, non-B was compared to that of healthy controls. Following induction by Molt 4 leukemia cells (P less than 0.001) and influenza A/X31 virus (P less than 0.01), there was a significantly lower interferon alpha response in patients with chronic hepatitis B and chronic hepatitis non-A, non-B. Yields of interferon gamma in patients with chronic hepatitis were comparable to those of normal individuals. The degree of interferon deficiency did not correlate with severity of liver disease. In patients with chronic hepatitis B, viral replication (presence or absence of HBeAg) was not related to the defect in interferon alpha production. Three of 10 patients with acute hepatitis B had measurable antiviral activity in the serum for 3-5 days after the onset of jaundice.