The plasma TSH response to TRH (200 μg iv) was investigated in a group of normal subjects of both sexes and in 108 patients with hypothalamic-pituitary disorders: 89 had pituitary tumors (49 had acromegaly, 36 had pituitary tumors without recognized hormonal secretion, 8 had craniopharyngioma, 1 had hypothalamic-pituitary metastasis from breast cancer, 1 had a hypothalamic- pituitary vascular tumor), 19 had other hypothalamic-pituitary disorders (1 Sheehan's syndrome, 4 primary empty sella, 12 idiopathic hypopituitarism, 2 idiopathic diabetes insipidus). Seventy-two were euthyroid; 32 had secondary hypothyroidism, 4 were thyrotoxic. The pattern of TSH response to TRH was defined with respect to the magnitude of the increase and to the pattern of the response curve. Three thyrotoxic patients did not respond to TRH, while one patient with high basal TSH values had a poor increase. Most of the other patients (88%) showed positive responses and the percentage of absent responses in euthyroid and hypothyroid patients did not significantly differ. Exaggerated responses were more frequently observed in hypothyroid patients (mostly in nontumorous cases). Regular response curves were observed in 55% of euthyroid and in only 19% of hypothyroid patients in whom there was a higher incidence of either delayed or prolonged response (56% and 37%, respectively). Frequently, prolonged responses were, at the same time, delayed and exaggerated. The incidence of these abnormalities was larger in patients with craniopharyngioma, in patients with pituitary tumors with suprasellar extension and in patients with idiopathic hypopituitarism. Therefore, these abnormalities can be considered quite characteristic of hypothalamic disorders.