1) Thirty days after surgical thyroidectomy, one group of rats were made diabetic by treatment with streptozotocin and were studied for the next 14 days. These diabetic thyroidectomized animals were similar in body weight to their thyroidectomized controls but had higher plasma concentrations of most amino acids. 2) Treatment with 0.5, 1.0 or 2.0 µg of L-thyroxine/100 g body wt for 7 days prior to sacrifice produced no changes in either parameter in the diabetic thyroidectomized animals. On the contrary, in thyroidectomized controls, the Lthyroxine treatment was followed by a dose-dependent increment in body weight. In these animals, the administration of 0.5 µg of L-thyroxine per day was associated with a marked rise in the plasma level of most amino acids, while only basic amino acid levels increased with 1.0 µg, and levels decreased with 2.0 µg. 3) In the diabetic thyroidectomized rats treated with insulin for the last 7 days before sacrifice, body weight gain and the biphasic change of plasma amino acid levels were restored. 4) It is proposed that treatment of thyroidectomized controls with small doses of L-thyroxine accelerate protein breakdown accompanied by minor changes in amino acid utilization, while this latter effect increases with higher doses of the hormone. 5) Present results demonstrate that a certain amount of circulating insulin is required to obtain the response to exogenous thyroxine in diabetic thyroidectomized animals. Results are discussed in terms of the role of interhormone synergism as it affects normal sensitivity of the different hormones.