A 34-year-old woman and a 54-year-old woman were treated with interferon-alpha (IFN-alpha) for chronic hepatitis C. Three months after the cessation of the IFN-alpha therapy, each patient developed hypothyroidism with the presence of thyroid-stimulation-blocking antibody (TSBAb) and TSH-binding inhibitor immunoglobulin (TBII). These two patients were treated with thyroxine, and both TSBAb and TBII activities gradually decreased. Although both TSBAb and TBII became negative several months after the start of the replacement therapy, the replacement dosage of L-thyroxine could not be reduced. Thyroid biopsies showed that the follicular epitheliums were flattened in both cases with lymphocytic infiltration. These findings suggest that IFN-alpha may induce hypothyroidism and the transient emergence of TSBAb and TBII.