OBJECTIVE The efficacy and side effects of interferon (IFN) therapy have not been well clarified in hemodialysis patients with chronic hepatitis C. METHODS In 6 of 9 hemodialysis patients with chronic hepatitis C, 3 million units (MU) or 6 MU of recombinant IFN-alpha2b or natural IFN-alpha were administered intramuscularly daily for the first 2 weeks, followed by three times a week for 22 weeks. In the remaining 3 patients, 3 MU of IFN-alpha2b were given three times a week for 24 weeks. Serum concentrations of IFN-alpha2b were measured sequentially after the injection of interferon. Responders were defined as the patients with normal serum aminotransferase and negative serum HCV RNA 6 months after the cessation of IFN therapy. RESULTS Three of the 6 patients who were administered IFN daily in the first 2 weeks were responders, while the other 3 withdrew from the therapy due to serious adverse events such as depression, loss of consciousness and persistence of high-grade fever. Serious adverse events were not observed in the 3 patients without daily administration. Half-lives of IFN-alpha2b in hemodialysis patients were significantly longer than those in nonuremic patients (10.0 vs. 6.0 h, p < 0.05). Moreover, the areas under the serum concentration curve of the hemodialysis patients were significantly larger than those of nonuremic patients (756 +/- 223 vs. 324 +/- 223 IU.h/ml, p < 0.05), despite the fact that the dose of IFN-alpha administered to hemodialysis patients was half that administered to nonuremic patients. CONCLUSIONS In hemodialysis patients with chronic hepatitis C, pharmacokinetic parameters of IFN may be different from those in nonuremic patients, and daily or high-dose administration of IFN may lead to serious adverse events in those patients.