Thirty-nine hemophiliac patients, negative for human immunodeficiency virus, with chronic hepatitis C who failed to respond to interferon (IFN) at 3 million units (MU) given subcutaneously thrice weekly for at least 3 months were retreated with 5 MU IFN for 6 months followed by 3 MU IFN in combination with daily oral doses of 1 or 1.2 g ribavirin. Thirty-four patients (87%) completed the study. In 4 patients treatment was discontinued because of treatment-related symptoms; 1 patient dropped out. Dosage reduction was required in 10 patients (26%) because of ribavirin-related anemia or IFN-related side effects. By intention-to-treat analysis, 14 (37%) had a sustained virologic response with preference for those infected by genotypes other than type 1 (43% versus 12%) and with high transaminases levels (168 U/L versus 116 U/L). Thus, IFN and ribavirin combination therapy led to a sustained suppression of hepatitis in one third of hemophiliac patients resistant to conventional monotherapy.