In 1981, we initiated combination therapy of short-term prednisolone withdrawal and adenine arabinoside (ARA-A) or interferon (IF) for the treatment of chronic hepatitis B. Long-term follow up (range 12-48 months) of 79 HBeAg-positive patients showed that at 24 months serum HBeAg was still positive in 77% of controls, 73% of patients receiving ARA-A or IF alone, 38% of patients receiving prednisolone withdrawal alone, and 25% of those receiving the combination therapy. The long-term follow up study revealed that the combination of an immunomodulating therapy and antiviral agents appears more effective in reducing hepatitis B virus replication than single agent treatment.