Ribavirin, an oral nucleoside analogue being evaluated as therapy for chronic hepatitis C, is associated with hemolysis. Other hemolytic conditions are known to be associated with accumulation of iron within the liver. We therefore examined hepatic iron stores before and after 6 to 12 months of therapy with ribavirin in 15 patients with chronic hepatitis C. Although there were no significant changes in serum iron or ferritin levels, hepatic iron staining increased in almost all patients. Using a ranking system to quantitate the amount of hepatic iron staining, we found that the mean rank increased from 3.9 to 8.5 after therapy (p < 0.01). In six patients in whom hepatic tissue was available for determination of hepatic iron, concentrations also increased in all cases from a mean of 826 to 1857 micrograms/g dry weight (p < 0.01). The average rate of iron accumulation in these six patients was approximately 1500 micrograms/g per year. Thus hepatic iron concentrations might enter the range clearly associated with hepatic fibrosis after approximately 15 years of continuous therapy.