A 25-year-old male physician with acute hepatitis C after needle-stick injury was treated with combination therapy including twice-a-day interferon-beta (IFN-β) and standard interferonalpha (IFN-α). The infecting strain was of genotype 1b. Pre-treatment hepatitis C virus (HCV) RNA levels were high. Because severe paresthesias occurred with initial daily administration of 5 million units (MU) of lymphoblastoid IFN-α, the dose was reduced to 3 to 6 MU of IFN-α2b three times a week. However, HCV RNA was not cleared from serum after 20 weeks of standard IFN-α2b treatment. A 4-week course with IFN-β, at the dosage of 3 MU twice daily IV drip, was then started and followed by an 18-week course with IFN-α2b, 6 MU thrice weekly. After IFN-β treatment, HCV RNA was cleared from serum without severe adverse effects, including paresthesias. Total amounts of IFN administered were 20 MU of lymphoblastoid IFN-α, 648 MU of IFN-α2b, and 252 MU of IFN-β. Complete response and avoidance of chronic HCV infection were achieved. Thus, combination therapy with twice-a-day IFN-β and standard IFN-α was effective in treating an acute hepatitis C patient with a high viral load and sensitivity to adverse effects of high-dose IFN-α.