The efficacy of a combination therapy of interferon (IFN) alpha-2b plus ribavirin (RBV) in chronic hepatitis C, and the factors contributing to efficacy, were investigated. One hundred eighty-six cases were enrolled in this study and treated with a combination of IFN alpha-2b plus RBV. IFN alpha-2b was administered at 6-10 mega-units daily for 2-4 weeks and three times per week for 20-22 weeks, in combination with oral intake of RBV at 600 or 800 mg for 24 weeks. Rates of sustained virological response (SVR) were 34.9% in serogroup 1 (SG1) and 82.5% in SG2. SVR rates in cases with both drugs discontinued, reduced, and unchanged were 4.2%, 40%, and 42.7% in SG1 and 42.9%, 76.9%, and 91.9%, in SG2. In terms of the total RBV dose per kilogram body weight, SVR rates were 14.3% and 46.2% with <1600 mg, 36.2% and 91.7% with 1600-2000 mg, and 62.1% and 95% with > or =2000 mg in SG1 and SG2, respectively. Total doses of RBV per body weight and negative HCV RNA at 8 weeks were the significant factors contributing to SVR in SG1 cases. These results indicate that it was critical to tailor the doses of RBV and IFN to the individual. To improve the rate of SVR, it is necessary to make efforts, where possible, not to discontinue drug use or reduce the drug dose.