To determine whether children with insulin-dependent diabetes mellitus (IDDM) might have exaggerated hormonal responses to hypoglycemia, the euglycemic-hypoglycemic glucose clamp procedure was used to provide a uniform hypoglycemic stimulus (plasma glucose kept at 90 mg/dL for 2 hours, then reduced to 50 to 55 mg/dL for 1 hour) in children and adults with and without IDDM. The chidren with IDDM showed an exaggerated rise in plasma epinephrine levels (625 +/- 112 pg/mL) compared with adults with IDDM (259 +/- 57 pg/mL, P less than 0.02); the same was true for children and adults without IDDM (811 +/- 100 vs 458 +/- 85 pg/mL, P less than 0.05). Among the children, the increase in epinephrine during hypoglycemia was similar in prepubertal and pubertal patients. Children with IDDM showed a greater rise in plasma norepinephrine than did adults with IDDM (P less than 0.001), and both diabetic groups failed to mount a glucagon response. Growth hormone and cortisol responses were unaffected by either childhood or diabetes. Enhanced secretion of epinephrine, induced by mild reductions in plasma glucose, may contribute to the management difficulties characteristically observed in the young patient with diabetes.