Increased levels of antibodies to TSH receptors are thought to be a major cause of active Graves' disease or recurrence following therapy. It was recently reported that T4 administration during antithyroid drug treatment for Graves' disease resulted in a significant decrease of TSH receptor antibodies compared to drug therapy alone. It is known that these antibodies may remain elevated long after patients become euthyroid, so a large number of patients whose antibodies remained significantly elevated after 1 year of methimazole therapy were evaluated in the study. A total of 330 Graves' disease patients were treated with methimazole for 1 year. TSH receptor antibody titers remained persistently elevated in 195 patients. Thirty-five randomly selected patients were continued on maintenance doses of methimazole for a second year, and 160 patients were treated with a combination of methimazole and thyroxine for a second year. T4 doses needed ranged from 75-100 micrograms/day to maintain serum-free T4 and free T3 within the normal range. After 6 months of combined therapy, 35 patients were found to have suppressed serum TSH levels. The patients were divided after 18 months into three groups: A, B, and C. Group C, consisting of 35 randomly selected patients (8 males and 27 females) whose ages ranged from 12-62 years and who had been maintained on methimazole alone, served as controls. Group B, whose serum TSH levels were suppressed after 6 months of combined therapy, consisted of 9 males and 26 females whose ages were 15-66 years. Group A, 35 randomly selected patients with normal serum TSH levels after methimazole and thyroxine therapy for 6 months, consisted of 8 males and 27 females whose ages were 10-63 years. TSH receptor antibody titers gradually decreased in all three groups with drug therapy, and there was no significant difference in the titers at corresponding times, i.e. 0, 1.0, 1.5, and 2.0 years. After treatment for 2.0 years, all patients of the three groups were followed for a further 12 months. Rates of recurrence among the above three groups were not significantly different during the observation period. In the present study, T4 administration in combination with antithyroidal drugs had no effect on levels of antibodies to TSH receptors and no effect on rates of recurrence. The reason for the discrepant results in the present study from previous reports is not known.