Thirty-six patients with hepatitis C virus-RNA positive chronic hepatitis were studied to evaluate whether recombinant alpha-2b interferon, in medium-high doses, (6-9 MU 3 times/week) over a long period (12-18 months), was more effective in reducing or normalizing alanine aminotransferase values, and in reducing the relapsing percentage than the historical trials. At the end of the 12th and 18th month of treatment, mean alanine aminotransferase values were significantly reduced; the level of complete responses was 36.1%, at the end of the 12th month, and 19.4% at the end of the 18th month (intention to treat). These results were no better than comparable findings in the literature. At the end of the first follow-up (12th month), percent complete responses fell to 15.5%, with a relapse rate of 14.3%. At the end of the second follow-up (24th month), percent complete responses fell further to 11.1% (all 4 patients with a 24 months sustained response showed absence of viraemia), with a relapse rate of 42.9%; even these percentages were judged unsatisfactory. In conclusion, no significant advantage was obtained by prolonging interferon treatment and/or using higher dosages. However, the possible virus clearance in all the long-term responders seems to justify further investigation in terms of cost-benefit analysis.