Combination therapy of interferon-alpha2b and ribavirin was prospectively evaluated in 20 patients with chronic replicative hepatitis and persistently normal ALTs. Patients with normal ALTs on three or more occasions within 6 months received interferon-alpha2b 3 MU three times a week with ribavirin 1000-1200 mg everyday for 12 months and had a follow-up of 6 months. HCV genotype 1 was found in 16, and HCV genotype 2 or 3 in 4 patients. No patient experienced an ALT elevation during therapy. Ten of 20 patients (50%) cleared virus at the end of treatment. In an intent-to-treat analysis, a sustained virological response (SR) was achieved in 8 of 20 patients (40%). Nonresponse occurred in 5 patients. Relapse and breakthrough were seen in 2 patients each. Treatment was discontinued in 3 patients due to side effects. Interferon (IFN) ribavirin combination therapy is effective in patients with normal ALTs and appears superior to IFN monotherapy.