Summary. Therapy with ribavirin for 6–12 months is associated with decreases in serum aminotransferases in some patients with chronic hepatitis C. We have assessed the practicality and safety of prolonged therapy with ribavirin. Six patients with chronic hepatitis C were given 1000–1200mg of ribavirin daily for 24 months. Serum aminotranferases and hepatitis C virus (HCV) RNA levels were monitored during and after therapy. Liver biopsies were carried out before and at the end of treatment. With therapy, mean serum alanine aminotransferase (ALT) levels fell from 161 U/L to 45 U/L at 12 months and to 39 U/L at 24 months. HCV RNA levels did not change. Liver histology improved in five and was unchanged in one patient. When therapy was stopped, aminotransferases rose to pretreatment levels. Side effects included mild fatigue and headaches. Two patients developed gallstones during therapy, perhaps caused by the chronic haemolysis that occurred in all patients. In conclusion, prolonged therapy with ribavirin can result in sustained improvements in serum aminotransferases and hepatic histology in a proportion of patients with chronic hepatitis C. Ribavirin therapy does not cause decreases in viraemia and, therefore, probably must be continued indefinitely to provide lasting benefit. The advantages of such therapy must be weighed against possible long-term side-effects.