In normal humans glucagon plays a primary role in promoting glucose recovery from hypoglycemia, glucagon deficiency is largely compensated for by enhanced epinephrine secretion, and recovery from hypoglycemia fails to occur only in the absence of both glucagon and epinephrine. Defective glucose counterregulation is exemplified by patients with insulin-dependent diabetes. Although most such patients have deficient glucagon secretory responses to hypoglycemia, they counterregulate adequately because of intact epinephrine secretion. Some patients, however, become defenseless against hypoglycemia because of combined deficiencies of glucagon and epinephrine.