Twenty patients with chronic B hepatitis and viral replication were included in a randomized study comparing the efficacy of sequential treatment with prednisone for 6 weeks followed by alpha-2a interferon (IFN) for 6 months (group A, 9 cases), versus concomitant administration of both drugs (group B, 11 cases). There were no significant differences between the two groups regarding age, sex, AST, ALT, DNA-VHB values, index of histological activity or type of underlying chronic hepatitis. Two patients from each group were excluded. The mean follow-up of the patients was 22.2 months. In group A, four responses were achieved (57.1%), of which 2 were complete and 2 partial. The overall response rate in group B was 77.7% (7 cases), 6 of them were complete responses (66.7%). Among HBsAg-positive patients from group B, one seroconverted to anti-HBs. A total of 7 patients with anti-HBe were included in the study. Two belonged to group A, in which a partial response was achieved, and another 5 were in group B, with 4 reaching a complete response and one reaching a partial response. There were no statistical differences with regards to the type of response in both groups. The AST, ALT values, as well as the pre-treatment levels of DNA-VHB, showed a significant statistical association with the response (p < 0.05). In all patients responding to treatment a histological improvement was observed that became even more evident in the biopsy performed 12 months after IFN withdrawal. In conclusion, concomitant therapy with prednisone and IFN is as effective as sequential therapy in the treatment of chronic B hepatitis. The results achieved with concomitant therapy suggest that new controlled trials are need to establish if this therapeutic schedule is the elective treatment in chronic B hepatitis.