Sequential liver biopsies were taken from 66 patients with chronic hepatitis B virus (HBV) infection being followed in randomised controlled trials of therapy with alpha interferons or adenine arabinoside 5'-monophosphate. In the group of 23 patients responding to treatment with the permanent loss of HBe antigen and HBV-DNA from their serum, there was a significant reduction in hepatic inflammatory activity and none developed cirrhosis. In contrast, inflammatory activity continued in the group of 24 patients that did not respond to therapy, and in the group of 19 patients who received no therapy. Two untreated controls progressed to cirrhosis. Further studies confirmed that in those clearing HBeAg and HBV-DNA from the serum, HBcAg and HBeAg were also lost from the liver. This study demonstrates that, as in natural seroconversion, successful treatment of chronic HBV infection is associated with loss of hepatic as well as serum markers of HBV replication, and is followed by a reduction in hepatic inflammation. Antiviral therapy may prevent progression to cirrhosis in some cases.