Abstract OBJECTIVE: Therapeutic options are limited for chronic hepatitis C patients who have not responded to a course of interferon therapy. Recently, a 6-month course of amantadine was shown to result in a sustained virological response in chronic hepatitis C patients who were unresponsive to interferon therapy. The aim of this study was to evaluate the effect of rimantadine on chronic hepatitis C patients who had not responded to interferon therapy. METHODS: This was an open label trial involving 17 patients who were treated with rimantadine 100 mg b.i.d. for 6 months. Changes in serum aminotransferase activities and HCV-RNA levels were determined. RESULTS: Mean alanine aminotransferase activities and HCV RNA levels did not change significantly during therapy. HCV RNA remained detectable in all patients throughout therapy. Neurologic symptoms (headaches, nervousness, and dizziness) developed in 29% of patients. A total of 12% of patients required dose reduction after 12 wk of therapy because of dizziness. CONCLUSION: Rimantadine has no significant antiviral activity against HCV.