It has been demonstrated that conditions which result in a drop in blood glucose produce an elevation in plasma radioimmunoreactive glucagon (IRG). Our data show that the low fasting blood glucose of hypophysectomized or adrenalectomized rats, however, is accompanied by an abnormally high plasma level of IRG relative to the magnitude of the drop in glucose concentration. Oral glucose loading in these animals results in a hyperglycemia which is almost twice the magnitude of the blood glucose elevation observed in similarly treated intact animals. The depression of the IRG, however, in the hormonally insufficient rats is not commensurate with the hyperglycemia achieved. Hormonal replacement with growth hormone or ACTH in the fasting hypophysectomized animals suppressed the high plasma IRG previously observed. Cortisone administration had similar effects in fasted adrenalectomized rats. Plasma immunoreactive insulin (IRI) concentrations were also abnormal in the untreated hypophysectomized or adrenalectomized rats but were restored to normal by pituitary or adrenal hormonal replacement. These results suggest that insufficiency of either growth hormone or the cortical steroids leads to a blunting of the endocrine pancreatic response to changing blood glucose concentrations. (Endocrinology94: 671, 1974)