Clinical evaluation was conducted to ascertain whether thyrotropin receptor antibody (TRAb) in the normal range may still be involved in the regulation of thyroid function after prolonged treatment for Graves' disease. All patients (n = 33) were treated with antithyroid drugs for an average of 10.6 years and were under euthyroid conditions in which normal blood levels of tri-iodothyronine (T3) were significantly correlated with blood thyrotropin (TSH) levels, but not with titers of TRAb. A significant correlation was observed between TRAb titer and thyroid-stimulating antibody (TSAb) activity. In contrast, this correlation was not found in normal subjects. After administration of T3 (75 microg daily for 8 days), the patients showed increased levels of T3 with concomitant suppression of TSH levels. Under these conditions, linear regression analysis showed significant correlations of TRAb titer and TSAb activity with 24-h thyroid radioiodine uptake (r = 0.641 and 0.621 respectively, P < 0.01), in contrast to declining blood thyroxine levels. Moreover, the immunoglobulin G (IgG) of the patients precipitated to a greater extent than IgG from normal subjects a peptide consisting of the amino acid sequence near the terminus of the human TSH receptor. These findings indicated that TRAb at normal levels possessed significant unremitting activities on thyroid function despite long-term treatment in euthyroid patients with Graves' disease.