We compared the response and the relapse rates of HBeAb-positive patients treated with interferon-alpha for 6 or 12 months. Thirty-eight HBeAb-positive patients which chronic hepatitis B were randomly allocated into two groups: Group I (19 patients receiving 10 MU of recombinant interferon-alpha 2b three times a week for 2 months, followed by 5 MU three times a week for 2 months and then 3 MU three times a week for 2 months); Group II (19 patients receiving 10 MU of recombinant interferon-alpha 2b three times a week for 2 months, followed by 5 MU three times a week for 2 months and then 3 MU three times a week for 8 months). At the end of treatment, alanine aminotransferase normalization was higher but not more significant in Group I than in II (53% vs 26%), while hepatitis B virus DNA clearance was similar in both groups (21% in Group I vs 26% in Group II). However, at 12 months of follow-up, biochemical relapses occurred only in Group I (60% vs 0% in Groups I and II, respectively). Five complete responders cleared hepatitis B surface antigen at that time. In conclusion, prolonged treatment of HBeAb patients is efficient in reducing the biochemical relapse.