Thyrotrophin-releasing hormone (TRH) is present in the pancreas, mainly in the islets of Langerhans. We studied the effect of iv infused TRH on the plasma levels of pancreatic islet hormones in man, under different experimental conditions: 1) Arginine infusion. 2) Insulin induced hypoglycaemia. 3) Glucose clamp technique (maintainance of normoglycaemia by glucose infusion during insulin infusion). 4) TRH injection. Except for a minor inhibition of glucagon and pancreatic polypeptide following hypoglycaemic stimulation in one study, TRH had no significant effect on basal, stimulated or inhibited plasma glucagon, on insulin, somatostatin, pancreatic polypeptide or blood glucose. It is concluded that iv administration of TRH does not produce significant changes in peripheral plasma levels of pancreatic hormones. Application of techniques, which allow studies closer to the pancreatic islet, is probably necessary to assess the role of TRH in the regulation of endocrine pancreas.