The brittleness of 100 severe diabetics was calculated as the mean of differences of blood glucose between two consecutive days at four time points (fasting, one and two hours after breakfast, and two hours after lunch). Mean daily difference (MDD) had a unimodal distribution; 15 patients with a MDD greater than 100 mg/100 ml were classified as most brittle. There was no correlation between MDD and insulin requirement. The brittle diabetics received 26 to 48 units of insulin/day. The insulin-resistant patients had low MDD values. No difference was found between seven patients with brittle diabetes and seven stable matched controls in insulin-binding capacity or total insulin. In two groups of six patients each with brittle diabetes, it was found that the stable dosage caused less brittleness than a sliding-scale regimen and that routine injection of 4 units of regular insulin before meals slightly decreased the mean diurnal glycemia level but increased the number of hypoglycemias. In two brittle diabetics, the blood glucose level was stabilized on intravenously administered insulin infusion, and in these patients, meals caused only a moderate hyperglycemia.