HU is a serious complication in patients with IDDM. HU usually develops in patients with long-term IDDM (>10 yr) who maintain tight glycemic control. We encountered a 16 yr old male with an 8.5 yr history of IDDM whose glycemic control over the long term had been marginal. He presented with multiple episodes of severe hypoglycemia (loss of consciousness or seizure) without prodromal adrenergic symptoms. Over 3 months, the patient's insulin dose was decreased by 40% (from 1.0 to 0.6 U/kg/d), but severe hypoglycemia persisted. The patient was hospitalized, at which time physical examination revealed a fatigued adolescent with recent 3 kg weight loss. No abnormal pigmentation was noted. On the first morning of the admission, the patient woke up confused. Heart rate was 70 per min. Prior to routine morning blood glucose (BG) measurement, the patient developed a generalized, tonic-clonic seizure. Analysis of serum revealed: glucose = 41 mg/dl; cortisol = 1.0 mcg/dl; growth hormone = 20.7 ng/ml; epinephrine and dopamine, undetectable; norepinephrine = 253 pg/ml. Because of the low cortisol concentration, serum ACTH (3045 pg/ml; nl. 10-60) and adrenal antibodies (+ at 1:20) were obtained. A subsequent ACTH stimulation test showed no cortisol response. The patient was started on cortisone acetate (12.5 mg/sq. M/day). Within 2 weeks of starting therapy, increasing BGs warranted an increase in insulin dose to 1.0 U/kg/day. Severe hypoglycemia did not recur. Hypoglycemic episodes during this period were accompanied by typical adrenergic symptoms. Three weeks after starting cortisone replacement, an episode of hypoglycemia was induced under observation by administering a.m. insulin and withholding breakfast. The patient was observed to have tremors, diaphoresis and tachycardia over a period of 15 min during which serum glucose fell from 83 to 39 mg/dl. Analyses obtained at the time of symptomatic hypoglycemia still showed undetectable serum epinephrine. However, norepinephrine increased to 405 pg/ml. Although there was no apparent recovery of epinephrine response to hypoglycemia, cortisone replacement did ameliorate the HU, thus resulting in a significant clinical improvement. This case demonstrates that HU may herald the onset of Addison's disease in patients with IDDM.