Combination interferon-alpha (IFN-alpha) and ribavirin treatment has become standard therapy for patients with chronic hepatitis C and elevated transaminase levels (> 1.5 x upper limit of normal). No previous study has specifically examined the efficacy of this treatment in patients with normal transaminase values. In this pilot study, we treated 19 patients, with normal or near-normal ALT values on at least three occasions, and histologically mild disease, with induction IFN-alpha2b, 5 mega units daily for 4 weeks, then 3 mega units thrice weekly for 44 week, plus concomitant ribavirin 1000 mg or 1200 mg daily for 48 weeks. Nine of the 19 (47%) showed sustained virological response, defined as undetectable HCV-RNA at 24 weeks after the end of treatment. No ALT flares were observed in any patient. We conclude that combination induction IFN-alpha and ribavirin therapy may be effective in patients with normal-ALT, and appears not to induce flares of ALT activity. Controlled trials of this treatment in this subgroup of patients with hepatitis C are warranted.