To obtain further information on the mechanism of abnormal serum thyrotropin (TSH) responses to thyrotropin-releasing hormone (TRH) reported recently in patients with Graves' ophthalmopathy, we compared the serum prolactin (PRL) and TSH responses to TRH, 200 fig iv in 13 such patients, 9 of whom were euthyroid and 4 hyperthyroid on the basis of serum free T3 and free T4. Among the 7 patients who demonstrated subnormal serum TSH response to TRH (Group I), 3 were hyperthyroid (Group IA) and 4 euthyroid (Group IB). The net 2-hr PRL secretion response of 401,508 and 321 ng-min in the 3 Group IA patients, respectively, was below the normal range (696–7914). However, the mean (±se) PRL secretion response of the 4 Group IB patients, 1400 ± 221 ng-min, did not differ significantly from the corresponding normal value, 2392 ± 760. Similarly, 1 hyperthyroid (Group IIA) and 5 euthyroid (Group IIB) patients who had supranormal serum TSH responses to TRH demonstrated a clearly normal serum PRL response (2786 ± 702 ng-min, cf. normal N.S.). It is concluded that lactotrophs respond normally to TRH in euthyroid patients with Graves' ophthalmopathy and that the abnormalities in serum TSH response to TRH in these patients are due to mechanism(s) other than a generalized defect in TRH, receptors.