Interferon and ribavirin decrease necroinflammation in chronic hepatitis C with or without virological clearance; however, reversibility of fibrosis remains to be established. We evaluated the effect of combination therapy on virological and liver histopathological outcomes in 52 naive patients and 79 patients unresponsive to interferon monotherapy with predominantly genotype 1 chronic hepatitis C. One hundred four patients completed interferon and ribavirin treatment after 24-48 weeks. Fifty-six paired liver biopsies (mean biopsy interval 28 months) were assessed by the Ishak score. Sustained virological responses were 37% in naive patients and 22% in re-treated patients. In virological responders and nonresponders, fibrosis and necroinflammation scores decreased by -0.91 (P = 0.04) and -0.5 (P = 0.02) and by -2.8 (P = 0.001) and -0.66 (P = 0.06), respectively. Interferon and ribavirin had greater benefit on fibrosis when associated with clearance of HCV RNA. Treatment strategies in virological nonresponders who show fibrosis regression should include consideration of maintenance therapy, if such treatment eventually proves to benefit histological outcomes.