Treatment for hepatitis C virus infection is limited in patients not responding to traditional therapy. Amantadine is effective for influenza infections and has been studied in patients with hepatitis C. Our aim was to determine the efficacy and safety of amantadine and to study the viral kinetics following amantadine therapy. Twelve patients with detectable HCV antibodies received amantadine 100 mg, orally twice daily. Serial HCV RNA and ALT blood samples were drawn and adverse effects were evaluated. Mean HCV RNA levels did not decrease in the first 24 hr of amantadine therapy but did decline significantly by day 3, only to rebound by day 7. All HCV RNA levels remained detectable throughout therapy and were not different from baseline values. Thirty-three percent of the patients obtained normal ALT levels after the first 24 hr of treatment and levels remained within normal range throughout the study period. More than a third of the patients discontinued therapy due to severe adverse effects occurring within one to three months after initiating treatment. In conclusion, although amantadine therapy alone was not effective, it should be considered as an adjunctive form of therapy along with interferon and ribavirin.