In a pilot study 15 patients with cryptogenic chronic hepatitis non-A, non-B received human recombinant interferon alpha (rIFNa) at a dosage of 5 million units 3 times per week for periods of up to 4 months, followed by an additional 4-month course of treatment with 2 million units 3 times per week after an observed reduction in serum aminotransferase levels. Ten of the 15 patients demonstrated antibodies to hepatitis C virus (HCV). Pretreatment histological examinations revealed evidence of chronic aggressive hepatitis in 12 patients, 4 with signs of cirrhosis, and chronic persistent hepatitis (CPH) in the remaining 3 cases. Normalization of serum aminotransferase levels was documented in 9 patients (7 anti-HCV-positive), and a significant reduction occurred in 2 additional anti-HCV-positive cases. Follow-up biopsy at 8 months in 7 of the 11 responders documented improved histological findings in every case. Five patients with CAH in the initial study had discrete residual portal inflammation or mesenchymal reaction in the second histological examination. Clinical follow-up is currently at 12 month, and 3 anti-HCV-positive responders have normal aminotransferase levels. The data show that a subset of patients with chronic hepatitis C will demonstrate remission of disease after an 8-month course of treatment with rIFNa.