Somatostatin has been proposed as a regulatory peptide of nutrient entry and fuel homeostasis because of its ability to inhibit the release of substances involved in food digestion and metabolism. The aim of the study was to evaluate the somatostatin response to a test meal in type I diabetics at the clinical onset of the disease and after two months of intensive insulin therapy. Normal subjects and diabetics in good metabolic control showed a characteristic biphasic somatostatin rise after a test meal; this response was lacking in diabetics at the onset of the disease. The response of somatostatin to a mixed meal in normals confirms its involvement in nutrient digestion and metabolism. The lacking somatostatin response in newly diagnosed type I diabetics might be related to deficient GIP response to the test meal or to other factors such as the insulinopenia or metabolic derangement characteristic of the clinical onset of the disease.