Hepatitis C is usually treated with interferon or a combination of interferon and ribavirin, but these agents have numerous side effects, and interferon must be given by injection three time a week. An alternative oral medication would be a welcome advance for treating hepatitis C. Amantadine has been reported to have the potential to produce viral suppression in patients with hepatitis C. To gain further knowledge about the effects of amantadine on hepatitis C, we treated 24 patients for 3-12 months (average = 5.5 months; median = 4.5 months) with 100 mg amantadine twice daily. Twelve patients had stage 3 or 4 fibrosis on biopsy. Eleven patients had a fall in viral titer, but complete viral suppression was not seen in any patient. Three patients had no viral titer obtained after treatment, but their elevated transaminase levels did not change with treatment. Of the 15 patients with a decrease in enzyme levels, only two patients had normalization. Six patients had side effects during the treatment, but in only one was amantadine stopped solely because of side effects. Based on these results and a literature review, we do not believe amantadine is an effective single agent for the treatment of chronic hepatitis C.