Rats were thyroidectomized (T) and injected once daily with thyroxine (T4) or triiodothyronine (T3) ip; circulating thyrotropin (TSH) levels and TSH response to 100 ng of thyrotropin releasing hormone (TRH) iv, were measured in different groups of rats at several intervals after the last dose of T4 or T3. It was found that T rats on 1.8 mug T4 or 0.4 mug T3/100 g BW/day, response to TRH decreased after the injection of the hormone, maximum suppressive effect being found about 7-8 h after T4, or 4 h after T3. The response increased as T4 or T3 levels reached a nadir, in agreement with present views on TRH, T4, and T3 interactions at the pituitary level. The degree of TSH response to TRH appears as a sensitive parameter of T4 or T3 activity in this experimental model. However, in T rats on 0.2 mug T3/100 g BW/day, TSH response to TRH did not decrease, but actually increased, after the daily injection of T3. These animals appeared to be in a state of continuous thyroid hormone deficiency. The same 0.2 mug T3 dose effectively suppresses the elevated basal TSH levels of these animals. It is also capable of decreasing TSH response to 100 ng TRH in animals under more "euthyroid" conditions. These results in the T rats on 0.2 mug T3 are not easily fitted into the relatively simple model frequently described to explain TRH-T3 interactions and TSH secretion.