To assess the efficacy of therapy with the antiviral agent interferon in chronic hepatitis C (non-A, non-B hepatitis), we randomly assigned 166 chronic hepatitis C patients to treatment with either 3 million or 1 million units of recombinant interferon alfa-2b three times weekly for 24 weeks, or to no treatment. The probability of normalization or near normalization of the serum alanine aminotransferase levels after 6 months of interferon therapy was 46% in patients treated with 3 million units of interferon (p less than 0.001) and 28% in those treated with 1 million units (p less than 0.02), but only 8% in untreated patients. Serum alanine aminotransferase levels became completely normal in 22 of the 26 patients (85%) who responded to treatment with 3 million units of interferon and 9 of the 16 patients (56%) who responded to treatment with 1 million units. The patients who received 3 million units of interferon had histological improvement because of the regression of lobular and periportal inflammation. Relapse within 6 months after the completion of treatment occurred in 51% of the patients treated with 3 million units of interferon and 44% of those treated with 1 million units. We conclude that a 24-week course of interferon therapy is effective in controlling disease activity in many patients with hepatitis C, although relapse after the cessation of treatment is common.