To evaluate the hypothalamic-pituitary-thyroid axis in acromegaly, total and free thyroid hormones and TSH response to TRH were determined in 36 acromegalic patients. In 10 patients, rT3 and thyroxine binding globulin (TBG) were also assayed by radioimmunoassay. In 15 patients the TSH response to TRH was also studied after medical or surgical therapy of the acromegaly. In 34 patients total thyroid hormones were in the normal range whereas two patients had low serum levels of free thyroid hormones. Thirty-two of the acromegalic patients were euthyroid. However, only 43.7% of the euthyroid patients had a normal TSH response to TRH. Nine patients had a reduced TSH rise after TRH, whereas in 4 patients the response was exaggerated and 5 delayed. In all patients studied rT3 and TBG were in the normal range. After medical or surgical therapy of the acromegaly we observed improvement or normalization of the TSH response to TRH. In conclusion, the TSH response to TRH is frequently altered in acromegaly, whereas thyroid function is generally normal. Hypothalamic effects of GH hyperproduction may explain the alterations of TSH secretion in many cases in view of the normalization of TSH secretion after therapy of acromegaly.