The cause of susceptibbility of certain diabetic patients to severe hypoglycemia is not known. Because the awareness of hypoglycemia is heightened by catecholamine-mediated physiologic responses, deficient catecholamine secretion may cause frequent and severe hypoglycemia. Plasma epinephrine and norepinephrine were measured after insulin-induced hypoglycemia in 18 diabetic patients, nine with autonomic neuropathy, and in nine normal volunteers. Our results show that two thirds of patients with diabetic autonomic neuropathy have moderate to severe deficits in epinephrine secretion and that these patients have diminished or delayed subjective responses to low blood sugar and are at risk for developing severe hypoglycemia and its neurologic consequences.