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TRH and T3 suppression tests were performed on patients (124 cases) with Graves' disease who underwent radiation therapy. TRH test was performed at 4-6 months (Group I), 6-12 months (Group II), 12-24 months (Group III) and 24-50 months (Group IV) after final radiation therapy, and T3 suppression test was performed just after each TRH test. The response to TRH test was defined as positive when the basal TSH value was less than 2.0 muU/ml and the peak value was more than 6.2 muU/ml following TRH (500 mug) injection. T3 suppression test was performed by measuring the 24-hr thyroidal uptake of radioiodine after daily administration of 75 mug of T3 for 8 days. The response was defined as positive when the value for 24-hr uptake after T3 administration was less than half of the control value. The results were as follows; 1) Among 124 patients in Group I to IV who were clinically euthyroid and whose T3-RU and T4 values were normal, compared with other groups, Group IV (2-4.2Y) showed a significantly higher percentage of positive responses to both TRH and T3 suppression tests. However, among 49 of 124 patients whose T3 was also normal, there were no significant differences between the groups. 2) The value of triiodothyronine was above the normal range in many cases up to 2 years after radiation therapy (in Group I, II, III). 3) There were no significant differences in the percentage of hyperresponses between any of the four groups. Half of the patients who showed positive responses to TRH test showed exaggerated responses. 4) In all cases when the responses to TRH and T3 suppression tests changed from negative to positive, thyroxine and triiodothyronine concentrations must be within the normal range. In particular, the major determinant seems to be the value of triiodothyronine. 5) As in more than 30% of cases TRH and T3 supression tests changed from negative to positive, thyroxine and triiodothyronine concentrations must be within the normal range. In particular, the major determinant seems to be the value of triiodothyronine. 5) As in more than 30% of cases TRH and T3 suppression tests remained negative even though their T3-RU, T4, T3, values became normal after radiation therapy, the regulation of hypothalamo-hypophyseal thyroid axis do not always return to normal even though circulating thyroidal hormone level return to an euthyroid state.