One hundred twenty-five patients with chronic hepatitis C were treated with natural IFN alpha or recombinant IFN alpha-2a, daily doses of 3 MU or 9 MU, respectively. IFNs were given 6 times a week for the first 2 weeks followed by thrice weekly administration for 12 weeks or more. ANA, TMA, AMA and anti-DNA antibody newly developed in 8, 1, 2 and 1 patient, respectively. Furthermore, we encountered some cases in which underlying autoimmune disorders were thought to be exacerbated by IFNs. It is important to pay sufficient attention to the development of autoimmune diseases in IFN therapy for chronic hepatitis C.