Summary. Interferon alpha therapy of hepatitis B virusrelated decompensated cirrhosis with the dose and the duration generally used is frequently associated with severe side-effects and reactivations. Between 1989 and 1996, 15 patients with hepatitis B virus-related decompensated cirrhosis received prolonged (3–48 months) low-dose (3 million units) IFN-α therapy. Ten patients (66%) had a sustained loss of serum hepatitis B virus DNA and hepatitis Be antigen (if present initially) associated with a decrease of aminotransferase levels into the normal range. During follow-up of these 10 patients, seven had a marked clinical improvement and are alive and fully active. One has an hepatocellular carcinoma, and two died without reactivation. Among the five other patients, two had a transient loss of serum HBV DNA followed by reactivation and three did not respond to therapy. During follow-up, one of these five patients died and one underwent liver transplantation. Severe complications, possibly related to interferon were uncommon and included bacterial infection in one case and variceal bleeding in two cases. Eleven of the 15 patients treated are alive after 1.5–7 years of follow-up. Hence, in patients with hepatitis B-related cirrhosis, prolonged low-dose IFN-α therapy is relatively well tolerated and may induce a sustained inhibition of hepatitis B virus replication with marked clinical improvement.