Insulin was administered to dogs in which an indwelling adrenal vein cannula had been placed. Blood glucose and adrenal venous 17-hydroxycorticosteroids (17-OHCS) were measured at frequent intervals during the following hour. The point at which adrenocortical stimulation was first seen following insulin does not correlate well with the absolute blood glucose concentration. The rate of blood glucose fall was of importance in the elicitation of the adrenal response, but at higher initial blood glucose levels a greater rate of blood glucose fall was necessary. The determinant which correlated best with whether adrenal 17-OHCS secretion would be stimulated was the rate of blood glucose fall as a function of the absolute blood glucose concentration at the time of insulin administration. Hypophysectomized animals did not show an increased adrenal 17-OHCS response following insulin administration. The present report suggests that the rate of blood glucose fall is one of the primary determinants in mediating the ...