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ObjectiveTo evaluate the response to treatment with interferon alfa and the long term outcome of patients with chronic active hepatitis B. MethodsSixty‐two patients with chronic active hepatitis B (43 males, 19 females; age range, 10‐67 years) who were treated with interferon alfa at Westmead Hospital between 1984 and 1992 were followed up (mean period of follow‐up, 44 months). Thirty‐nine patients were treated with interferon alfa‐2a and 23 with interferon alfa‐2b for a mean of 22.5 weeks. Interferon was given three times a week with a dose range of 3‐21 million U. We evaluated pretreatment predictors of response (patient's age, sex, ethnic origin, presence of cirrhosis, serum levels of alanine aminotransferase [ALT] and hepatitis B virus DNA [HBV‐DNA]) and the effect of dose and type of interferon. ResultsNine patients had a complete response to treatment with interferon alfa (loss of hepatitis B surface antigen), 26 had a partial response (permanently HBV‐DNA negative, hepatitis B e antigen to anti‐hepatitis Be seroconversion), eight had a transient response and 19 had no response. All patients with a complete response had normal ALT levels at last follow‐up. Histological evidence of hepatic inflammation was significantly reduced in responders. A high pretreatment ALT level and a low HBV‐DNA titre were both positive predictors of a favourable response. We found no significant difference in the response to different types of interferon or to high or low dose regimens, or in the responses of patients with cirrhosis. ConclusionTreatment with interferon alfa was associated with prolonged suppression of HBV replication in over half these patients and 14% appear to have been cured of the infection. Suppression of HBV replication is associated with sustained abatement of liver disease.