Somatostatin is found in the D-cells of organs that are exclusively responsible for the digestion, absorption, and metabolism of ingested nutrients. D-cells apparently release their secretory products both into the interstitial space (paracrine action) and into the circulation (endocrine action). Ingestion of all three basic nutrients--fat, carbohydrate, and particularly protein--elicits a significant increase in peripheral vein plasma somatostatin levels in dogs and humans. Acidification of a meal stimulates somatostatin release in dogs. Vagal, cholinergic, and adrenergic mechanisms exert a species-dependent effect on somatostatin release. Gut hormones also participate in the regulation of postprandial somatostatin release, and endogenous opioids have an effect that depends on the composition of the meal. Stimulation of postprandial somatostatin release by H2-receptor agonists and prostaglandins has been reported. Insulin inhibits and glucagon stimulates somatostatin release. Elevated levels of circulating glucose reduce the somatostatin response, an effect that cannot be entirely explained by the parallel augmentation of insulin secretion. Circulating nutrients also modify the effect of gut hormones on D-cell function. The physiological action of somatostatin is an inhibitory effect on virtually all gastrointestinal and pancreatic exocrine and endocrine functions. Secretory and/or motor activities are attenuated, thereby preventing an exaggerated and overshooting response. Alterations of tissue somatostatin content and plasma somatostatin levels have been observed in obesity and suggest that somatostatin deficiency may be a pathogenic factor. The observed changes of somatostatin may be secondary to alterations of other functions; nevertheless, hyposomatostatinaemia might facilitate nutrient assimilation.