To study whether interferon (IFN) alpha and ribavirin combination therapy has a beneficial effect for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, we enrolled 119 such patients in a randomized study. Fifty-nine patients received 5 million units of IFN-alpha2b daily for 4 weeks followed by 5 million units three times a week for 28 weeks, plus 1,200 mg ribavirin daily. Sixty patients received the same dosage of IFN plus placebo. They were followed up for 24 weeks posttreatment, and 105 patients (88%) completed the entire course of 56 weeks. By intention-to-treat analysis, the rate of combined response (serum hepatitis B virus [HBV] DNA <2.5 pg/mL and HBeAg seroconversion) was 17% versus 25% between the IFN/ribavirin and IFN/placebo group, respectively, at the end of treatment (P = .35) and 25% vs. 20% at the end of follow-up (P = .32). Using quantitative real-time polymerase chain reaction assay, the log10 reduction of serum HBV DNA was 1.05 +/- 1.72 (mean +/- SD) versus 1.29 +/- 1.91 between the two groups at the end of treatment (P = .49) and was 2.15 +/- 2.15 versus 1.21 +/- 2.48 at the end of follow-up (P = .04). Prolonged observations in 83 patients suggested that the combined response was 29% (n = 17) versus 20% (n = 12) at 48 weeks after the end of treatment, respectively (P = .17). The safety profile was similar, except that the IFN/ribavirin group had a higher risk of anemia (15% vs. 0%; P = .002). In conclusion, for the treatment of HBeAg-positive chronic hepatitis B, adding ribavirin does not seem to increase the efficacy of IFN.