The insulin-induced hypoglycemia test was used to study the hypothalamic-pituitary function of nine normal control subjects and 49 patients with amenorrhea. There were 10 patients with secondary amenorrhea due to hypothalamic dysfunction, eight with hypothalamic failure, eight with primary amenorrhea due to hypogonadotropic hypogonadism, 19 with a prolactin-secreting pituitary adenoma, and four with Sheehan's syndrome. After the administration of insulin (0.15 unit/kg), a significant increase in plasma levels of prolactin, growth hormone, and cortisol occurred in all normal subjects. Of the 10 patients with hypothalamic dysfunction, two had a blunted prolactin response, six had an abnormal growth hormone response, and all had a normal cortisol response. Of those with hypothalamic failure, abnormal responses for prolactin were seen in two patients, for growth hormone in four patients, and all had a normal increase in cortisol. Five of the eight patients with primary amenorrhea had a blunted response for prolactin, six for growth hormone, and there were no abnormalities for plasma cortisol. All 19 patients with pituitary adenomas had a blunted increase in prolactin, 16 had an abnormal growth hormone response, and two had an abnormal cortisol response. Prolactin, growth hormone, and cortisol responses were blunted in all patients with Sheehan's syndrome. These results demonstrate that the release of growth hormone subsequent to insulin-induced hypoglycemia is the most common abnormality seen in women with amenorrhea. The high frequency of abnormal release of prolactin indicates that serum prolactin should be measured when this test is performed. In addition, patients with prolactin-secreting adenomas and those with Sheehan's syndrome should be given an insulin tolerance test before treatment is instituted, so that patients with secondary adrenal insufficiency can be identified.