It is commonly accepted that hypothalamic dopamine has an inhibitory role not only on prolactin but also on TSH secretion. To study the hypothalamic dopaminergic participation in TSH secretion in various hypothalamo-pituitary disorders, we examined the effect of sulpiride, a dopamine antagonist. Using a commercially available human TSH radioimmunoassay (RIA) kit and improving it, we developed a high sensitivity RIA for human TSH (assay sensitivity: 0.15 micro Units/ml, 50% B/B0 values: 3.47 micro Units/ml). In 18 normal controls, plasma TSH increased significantly after intramuscular injection of sulpiride of 1.01 +/- 0.17 micro Units/ml (Mean +/- SEM). In 61 patients with pituitary adenoma, plasma TSH responses to sulpiride were significantly greater than those of normal controls, and the mean maximal increments were as follows: 1.65 +/- 0.24 micro Units/ml in acromegaly (n = 21), 2.63+/- 0.55 micro Units/ml in non-functioning pituitary adenoma (n = 23), and 4.49 +/- 0.70 micro Units/ml in prolactin producing pituitary adenoma (n = 17), respectively. The maximal TSH responses to sulpiride in prolactin-producing pituitary adenoma were significantly greater than those in non-functioning pituitary adenoma (p less than 0.05) and those in acromegalic patients (p less than 0.001). On the other hand, we could observe no TSH responses to sulpiride in 9 cases of hypothalamic tumor with hyperprolactinemia. These results suggest that the dopaminergic inhibitory influence on TSH secretion is increased in patients with pituitary adenoma, and that it is especially dominant in patients with prolactin producing pituitary adenoma. It is concluded that hypothalamic dopaminergic tone can be evaluated indirectly by the sulpiride test, and that the test is useful in the differential diagnosis of hypothalamo-pituitary disorders.