Ribavirin is a nucleoside analog that inhibits the replication of many DNA and RNA viruses. To evaluate the efficacy of oral ribavirin, we randomly assigned 24 HBeAg-positive patients with chronic active hepatitis to a 12-wk course of treatment with 0.8 to 1.0 gm/ribavirin day, 3 mU interferon-β three times a week intravenously or a combination of those drugs. Ribavirin, alone and in combination with interferon-β, decreased hepatitis B virus levels in most patients, and mean serum hepatitis B virus DNA and DNA polymerase levels at the end of treatment were approximately half of baseline levels (p < 0.05). Interferon alone exerted the most inhibitory effect on hepatitis B virus activity (p < 0.01). During ribavirin treatment, changes in serum aminotransferase values varied considerably and the mean values did not change significantly, although interferon alone and the combination of interferon and ribavirin were associated with significant reductions in serum aminotransferase activities. Ribavirin was well tolerated, but we transiently reduced the dosage in two cases because of mild hemolytic anemia, although all patients completed the treatment schedule. The combination of interferon and ribavirin did not appear to result in greater toxicity. During the follow-up period (6 to 9 mo), HBeAg and hepatitis B virus DNA disappeared in one patient treated with ribavirin, in two treated with interferon and in two given the combination. These results indicate that ribavirin suppresses hepatitis B virus replication, although its effect is less than that of interferon, and that it may be useful as adjunctive therapy for chronic hepatitis B. Simultaneous administration of ribavirin and interferon does not appear to potentiate the beneficial effect and may even inhibit the effect of interferon. (HEPATOLOGY 1993;18:258–263).