To evaluate the effect of strict glycemie control of insulin-dependent diabetes mellitus (IDDM) on the plasma glucose threshold initiating counterregulatory hormone responses to hypoglycemia, we used the glucose clamp technique to produce a standardized gradual glucose decline from 90 to 40 mg/dl in seven young IDDM patients before and after 2–6 mo of intensified insulin therapy. Before intensive therapy [hemoglobin A₁ (HbA₁) 9.6 ± 1.1%], epinephrine responses were triggered at a higher plasma glucose level (67 ± 4 mg/dl) than in normal control subjects (56 ± 1 mg/dl, P < .05), and clinical symptoms of hypoglycemia appeared at glucose levels of 50–60 mg/dl. After intensive therapy (HbA, 7.1 ± 0.7%), the glucose threshold for epinephrine release consistently declined to values (46 ± 2 mg/dl) below normal (P < .01). Furthermore, epinephrine concentrations were markedly reduced at each hypoglycemie level, and a greater hypoglycemie stimulus was required to elicit symptoms. The glucose threshold stimulating release of growth hormone also significantly declined after intensive therapy. We conclude that strict glycemie control of IDDM lowers the plasma glucose level required to generate epinephrine release during hypoglycemia. This may diminish patient recognition of moderate hypoglycemia and increase the risk of severe hypoglycemia in intensively treated IDDM.