Background/Aims: It has been suggested that hepatitis C virus is associated with the autoimmune disease and interferon also induces hepatic and non-hepatic autoimmune reaction. We conducted this study to assess the effect of interferon-alpha (INF-α) on the induction of thyroid autoantibodies and clinical thyroid disease and to know whether the thyroid autoantibodies affect the IFN-α efficacy in patients with chronic hepatitis C. Methods: Twenty-nine patients with chronic hepatitis C were enrolled. Anti-thyroglobulin antibody (ATA), anti-microsomal antibody (AMsA), thyroid stimulating hormone and free thyroxine were measured before, during, and after IFN-α therapy. Results: Two of the 29 patients (6.5%) were positive for ATA and AMsA before IFN-α therapy. Of these two patients, one patient was a woman, who showed hyperthyroidism druing IFN-α therapy. Of the 27 patients who had been negative for ATA and AMsA, one female patient became ATA positive with the development of hyperthyroidism, and 3 male patients became AMsA positive during IFN-α therapy. There was no difference in the efficacy of INF-α therapy between the thyroid autoantibody positive and negative groups. Conclusions: IFN-α therapy induced thyroid disease with high prevalence in the patients with chronic hepatis C. Thus, thyroid status should be checked even in patients without thyroid autoantibodies, especially in woman. Antithyroid autoantibodies seem unlikely to affect the efficacy of IFN-α therapy. (Korean J Gastroenterol 2001;37:436-442)