Many elderly people are treated with medications or are subjected to diseases which can cause hypoglycemia. We conducted the following studies to assess whether alterations in counterregulatory hormone release, decreased awareness of warning symptoms or alterations in psychomotor performance might increase the susceptibility of the elderly to hypoglycemia. Healthy, nonobese young (n = 10, age < 30) and old (n = 9, age > 65) subjects underwent paired hyperinsulinaemic clamp studies (insulin infusion rate 60 mU/m2.min). In the control study, glucose was kept at 5.0 mmol/L for 5 h. In the hypoglycemic study, glucose was kept at 5 mmol/L for 1 h and was lowered in stepwise fashion to 4.4, 3.8, 3.3, and 2.8 mmol/L in each subsequent hour. Subjects were blinded as to which study they were undergoing. Counterregulatory hormones were measured and a hypoglycemic symptom checklist was administered every 15 min in each study. Neuropsychological tests were performed at regular intervals. The glucose threshold for release of counterregulatory hormones was defined as the glucose level at which the values during the hypoglycemic study first exceeded values during the control study by 2 SD. The glucose threshold for glucagon and epinephrine release was higher in the young (approximately 3.3 mmol/L) than the old (approximately 2.8 mmol/L) and the epinephrine responses to hypoglycemia were also greater in the young. The threshold for release of GH (approximately 3.3 mmol/L) and norepinephrine and cortisol (approximately 2.8 mmol/L) was similar in each age group, as was the magnitude of release of these hormones. Although the variance in symptoms scores was large, the elderly appeared to have reduced awareness of the autonomic but not neuroglycopenic symptoms of hypoglycemia. There was no difference between young and old in the effect of hypoglycemia on neuropsychologic tests. We conclude that healthy elderly people may have impaired release of glucagon and epinephrine in response to hypoglycemia and reduced awareness of the autonomic symptoms of hypoglycemia.