A selective glucagon deficiency was documented in a 36-year-old female patient suffering from severe hypoglycemic attacks. The extremely low fasting plasma glucagon levels could not be stimulated by hypoglycemia. The increase in plasma glucagon during stimulation with arginine did not prevent hypoglycemia provoked by the simultaneous insulin secretion. Treatment consisting of a continuous sc glucagon infusion system resulted in correction of both postabsorptive and postprandial hypoglycemia. Further lowering of the glucose level during an arginine test could be the hallmark of this hypoglycemic syndrome characterized by an inappropriate glucagon secretion. This case report would indicate that epinephrine cannot prevent hypoglycemia when glucagon release is completely deficient.