BACKGROUND: Interferon (IFN) retreatment for hepatitis C virus (HCV) relapsers has been effective under some conditions. We conducted a randomized, controlled trial of IFN beta retreatment for HCV relapsers after IFN alpha. PATIENTS AND METHODS: We gave IFN beta 6MIU therapy to 43 patients who had relapse of HCV after the 24 weeks IFN alpha monotherapy. The 43 patients were randomly assigned to two groups: Group A started retreatment within 4 weeks after relapse; and Group B started retreatment 24 weeks or more after relapse. RESULTS: Nine patients showed sustained virological response (SR) to the retreatment. All of these patients were in a low viral load subgroup. The SR rate in Group A (8/22, 36%) was significantly higher than in Group B (1/21, 5%) (P=0.0128). Among patients with lower viral load, the SR rate in Group A (8/10, 80%) was also significantly higher than in Group B (1/8, 13%) (P=0.0076). CONCLUSION: The retreatment with IFN beta is effective for patients with HCV low viral load, and the sooner after the relapse the retreatment is started, the better the clinical results will be.