Treatment of chronic hepatitis C with interferon has been disappointing, with less than one-third achieving a sustained response and most experiencing significant side effects. A prospective open-labeled study was conducted to test the safety and efficacy of the anti-viral drug amantadine-HCL, in patients with chronic hepatitis C infection who had previously failed therapy with interferon. Patients were treated with amantadine-HCL 100mg given orally twice daily for six months. Thirty percent achieved a complete response (normalization of alanine aminotransferase, ALT, and loss of hepatitis C RNA), 40% a partial response (> 50% reduction in ALT and RNA), and 30% did not respond to amantadine-HCL. Response to therapy was significantly greater with amantadine-HCL compared to two time intervals of no treatment or therapy with interferon. The purpose of this study is to expand these findings to a larger trial designed as a randomized double-blind placebo controlled cross-over study. Eligible patients with hepatitis C will be randomized to receive either amantadine -HCL or placebo by mouth twice daily for six months. After six months, patients on placebo will be crossed over to amantadine treatment for the next six months and those on amantadine will be continued for an additional six months. Response to therapy will be assessed by a reduction in the hepatitis C viral RNA level and hepatic alanine aminotransferase levels.