To evaluate the response during insulin-induced hypoglycemia, diabetics treated with relatively selective or nonselective beta-adrenergic blocking agents were studied. Placebo, atenolol (100 mg/day), and propranolol (80 mg b.i.d.) were administered to 12 insulin-treated diabetics for 1 week in a double-blind, randomized, crossover fashion with a 2-week washout between treatments. Sufficient intravenous insulin (0.2-0.6 units/kg) was administered to decrease plasma glucose 68% from the basal level or to less than 60 mg/dl within 90 minutes. Blood pressure changes at the nadir of plasma glucose were +15.2/-9.9 mm Hg for placebo, +27.9/0 mm Hg for atenolol, and +38.8/+14.3 mm Hg for propranolol. Diastolic blood pressure changes induced by propranolol were significantly different from those induced by atenolol (p less than 0.01) and placebo (p less than 0.01), and systolic pressure changes were significantly different (p less than 0.02) between propranolol and atenolol. Mild seizures developed in two patients treated with propranolol. Their blood pressure changes at the plasma glucose nadir were +56/+22 and +86/+31 mm Hg. Other symptoms of hypoglycemia were more frequent during beta-blocker than during placebo treatment. Differences in response may be related to the relatively selective adrenergic blocking effect of these drugs.