After several years of insulin therapy, about 20% of insulin-dependent diabetics have little or no perception of hypoglycaemia because of a loss of the adrenergic warning symptoms. This defect, poorly correlated with the presence of autonomic neuropathy, has been classically explained by a defect in the catecholamine secretion. We compared the hormonal counterregulation during hypoglycaemia induced by subcutaneous injection of insulin in 7 insulin-dependent diabetics with poor perception of hypoglycaemia and experiencing repeated episodes of severe hypoglycaemia (group A) and 7 insulin-treated diabetics with very good perception of hypoglycaemia and not experiencing severe hypoglycaemia (group B). Groups A and B were similar in terms of age, duration of diabetes, HbA1c level and degenerative complications. The glucagon levels were identical and non-reactive in the two groups. The basal levels and secretion peaks of adrenaline, noradrenaline, growth hormone and cortisol were similar between the two groups, but there was a significant delay in secretion in group A with a blood glucose threshold of adrenergic secretion of between 3.1 +/- 0.5 and 1.6 +/- 0.2 mmoles/l in group A and between 4.6 +/- 0.3 and 3.2 +/- 0.2 mmoles/l in group B (P less than 0.05). This delayed secretion could be explained by desensitisation of the hypothalamic glucostat and could be due to the frequency and/or severity of hypoglycaemic episodes.