Somatostatin was originally isolated from the hypothalamus and has now been found in large quantities in the gastrointestinal tract and pancreas. Its localisation in nerve endings and endocrine-like cells suggests that somatostatin is a putative neurotransmitter and/or neuromodulator, local or paracrine acting substance and true endocrine factor or hormone. The present communication summarises the evidence for the release of somatostatin into the gastrointestinal lumen and the potential action of luminally released somatostatin. Furthermore, the evidence is presented for the release of splanchnic somatostatin into the circulation in response to a meal in rat, dog and man. The biological role of postprandially released and circulating somatostatin is to prevent an exaggerated response of certain exo- and/or endocrine functions of the gastrointestinal tract and pancreas as indicated by studies employing low-dose infusions of synthetic somatostatin or by neutralisation of somatostatin following the injection of specific antibodies. The release of gastric and pancreatic somatostatin is regulated by ingested and circulating nutrients and is modulated by neural mechanisms (cholinergic, adrenergic, dopaminergic) histamine, prostaglandins, opiates and gastrointestinal hormones. Several studies demonstrating a tight interaction between somatostatin and insulin indicate that insulin is another important factor in the regulation of basal and postprandial somatostatin release. The role of somatostatin in pathophysiological states such as peptic ulceration and diabetes mellitus is not entirely clear but the present evidence indicates that alterations of tissue somatostatin content or plasma somatostatin levels are secondary to changes of other factors (increased gastric acid secretion, insulin deficiency) rather than representing the primary cause for the underlying disease. Measurements of somatostatin in plasma are useful as a marker for the diagnosis of somatostatin-producing tumours.