The effect of the administration of oral glucose with or without a simultaneous intravenous somatostatin infusion on blood glucose, immunoreactive insulin, C-peptide, and glucagon levels in seven patients with idiopathic postprandial hypoglycemia was studied. Oral glucose alone induced an excessive insulin response and hypoglycemia, whereas a slight suppression in glucagon levels without any increase at the hypoglycemic nadir was observed. The simultaneous administration of somatostatin significantly reduced the insulin response and induced a slower rise of blood glucose; no hypoglycemia developed. Only minor variations in glucagon were observed with respect to the basal test. A rebound in insulin, C-peptide, and glucagon levels was observed at the end of the somatostatin infusion. These data show that somatostatin can suppress glucose-induced hypoglycemia in these subjects, thus suggesting that its long-acting analogues might be worth a therapeutic trial in severe idiopathic postprandial hypoglycemia.