We have tested the efficacy of prior stress-induced increases in corticosteroids on inhibition of the ACTH response to hypoglycemia induced 2 h later. Five dogs were studied in each of five experiments. In each experiment, there were two stimulus periods; in the first, 5% dextrose, 3 or 10 micrograms/kg X min nitroprusside, or 0.05 or 0.10 U/kg insulin was administered, and in the second, 0.10 U/kg insulin was administered. Whereas prior infusion of 5% dextrose did not affect the subsequent ACTH response to 0.10 U/kg insulin, prior stimulation of the pituitary-adrenal axis had a significant effect on the subsequent ACTH response to 0.10 U/kg insulin. The integrated ACTH response to hypoglycemia was significantly reduced by prior stimulation by either 10 micrograms/kg/min nitroprusside or 0.10 U/kg insulin, although the intensity of the hypoglycemia during the second stimulus period was not altered by any of the prior stimuli. Overall, the magnitude of the suppression of the pituitary-adrenal response to hypoglycemia was significantly related to the increase in plasma corticosteroids produced by the first stimulus, and was consistent with the degree of corticosteroid feedback inhibition of ACTH observed in previous studies after ACTH or corticosteroid infusion. Therefore, we conclude that prior stimulation of the hypothalamo-pituitary-adrenal axis of conscious dogs by hypotension or hypoglycemia inhibits subsequent responses in proportion to the corticosteroid feedback signal produced.