Counterregulatory hormone responses to hypoglycemia were examined in six healthy controls and in six patients with type I diabetes before and after 4 to 8 months of insulin pump treatment. The insulin clamp technique was used to provide an identical hypoglycemic stimulus (about 50 mg/dL) in each study group. Before pump treatment, the release of counterregulatory hormones (except glucagon) during the hypoglycemic period was not significantly different in diabetics from that in normal controls. However, when values before and after pump treatment in diabetics were compared, there were significant reductions in epinephrine (304 +/- 70 and 127 +/- 43 pg/mL; p less than 0.01), growth hormone (45 +/- 12 and 18 +/- 5 ng/mL; p less than 0.05), and cortisol (20 +/- 3 and 10 +/- 2 micrograms/dL; p less than 0.01) levels during hypoglycemia. Defective glucagon release during hypoglycemia in the diabetics was not corrected by pump treatment. Intensive insulin treatment of patients with type I diabetes causes a generalized reduction in counterregulatory hormone release after a moderate fall in blood glucose levels. This reduction may impair glucose counterregulation and diminish perception of hypoglycemia, thereby increasing the risk of hypoglycemic episodes.