Chronic hepatitis C patients (472 patients) were treated with consensus interferon (CIFN) or interferon (IFN) alfa-2b for 6 months in a large multicenter trial. Efficacy was assessed by clearance of hepatitis C virus (HCV) RNA using reverse transcription polymerase chain reaction (RT-PCR) (<100 copies/mL), normalization of serum alanine aminotransferase (ALT), and histological improvement. The purpose of these analyses was to compare these efficacy parameters in nonfibrotics, fibrotics, and cirrhotics. Patients with chronic HCV and cirrhosis showed the same benefit from IFN treatment as noncirrhotic patients when efficacy was assessed by clearance of serum HCV RNA or by histological benefit. Sustained HCV RNA response rates were similar when measured among nonfibrotic (11%), fibrotic (13%), and cirrhotic (11%) patients. Improvement in histologic activity index (HAI) scores was noted among all 3 groups. Cirrhotic patients had a lower sustained ALT response rate (12%) than did nonfibrotic patients (23%). Ninety percent of nonfibrotics, but only 71% of fibrotics and 67% of cirrhotics, who sustained a virological response normalized their ALT. This suggests that cirrhotic patients may clear the hepatitis C virus without normalization of ALT levels. The pattern of both HCV RNA clearance over time and ALT decrease was similar among nonfibrotics, fibrotics, and cirrhotics. Tolerability to IFN therapy was similar among the 3 groups except that more cirrhotics required dose reduction because of thrombocytopenia. In patients with cirrhosis, ALT levels may be a less appropriate endpoint in the measurement of response to therapy. We conclude that liver cirrhosis should not be a reason for excluding patients from therapy because both cirrhotic and fibrotic HCV patients benefit from IFN therapy not only by clearance of virus but by improvements in liver histology.