Interferon-alpha (IFN) has been accepted as an effective treatment for chronic hepatitis C virus (HCV) infection in hemodialysis (HD) patients. We prospectively assess the long-term clinical, biochemical, and virological effects of interferon in the treatment of HD patients with chronic HCV infection. This study was performed in 20 HCV-RNA-positive HD patients with evidence of chronic hepatitis on liver biopsy. The patients received IFN administered after HD sessions in doses ranging from 3 to 6 million units for 6 to 12 months. The patients were followed up for a period of 6 years with determinations of serial alanine aminotransferase (ALT) levels and serum HCV-RNA. At the time of the final follow-up, the patients had no cirrhosis or hepatocellular carcinoma. Among the nonresponder group, only 1 patient died due to sudden cardiac death. Sustained normal serum ALT levels occurred in 9 (45%) of the patients. Nine patients had variable ALT levels, and 2 patients had persistently elevated ALT levels. Eight (40%) patients were continuously HCV-RNA negative, whereas 12 patients (60%) had variable HCV-RNA results at the end of the 6-year follow-up. These findings show that the long-term clinical, biochemical, and virological response to interferon monotherapy is good in HD patients with HCV infection.