Pituitary function has been studied sequentially after transsphenoidal removal of pituitary microadenomas in two men with Cushing's disease. Patient 1 gradually regained normal glucocorticoid levels with normal diurnal variation, metyrapone responsiveness, and low dose dexamethasone suppressibility (17-hydroxycorticosteroid, 6.5-0.9 mg/24 h). GH levels rose from 1 to 35 ng/ml during insulin hypoglycemia and from 2.3 to 27 ng/ml during arginine infusion. PRL secretion rose normally in response to thorazine, and gonadotropin and TSH levels remained normal. Patient 2 regained significant metyrapone responsiveness by 9 months postoperatively (11-deoxycortisol rose to 11.7 micrograms/dl), had a normal spontaneous nocturnal rise in PRL secretion, and normal levels of testosterone and thyroid hormones. The return to normal of cortisol-ACTH dynamics and GH responsiveness in Patient 1 and the normal nocturnal surge in PRL secretion in Patient 2 imply that in these patients the etiology of Cushing's disease was not related to hypothalamic dysfunction.