Abstract: Gut hormones exert important effects on gut growth, secretion and motility and on intermediary metabolism, and may play a key role in the postnatal adaptations to enteral feeding. Using sensitive radioimmunoassays we have measured 10 entero-insular hormones in the plasmas of (a) 203 healthy term or preterm infants at birth, or during the first 24 days of life either before or at 30, 60 or 120min. after feeding and (b) 10 six-day old preterm neonates who had never been fed orally since birth on account of hyaline membrane disease. Each infant contributed, with ethical approval, only one plasma sample, removed at the time of a routine clinical blood test. Basal levels of gastric inhibitory polypeptide (GIP), pancreatic polypeptide (PP), enteroglucagon (EG), neurotensin (NT), motilin, and gastrin all rose steeply during the neonatal period, the latter four hormones reaching levels which exceeded significantly those seen in healthy fasting adults. In contrast plasma concentrations of GIP, EG, NT, motilin and gastrin did not show postnatal elevation in the unfed group of infants. In addition for 8 hormones; secretin, GIP, PP, NT, EG, motilin, gastrin and insulin, we observed a progressive postnatal increase in the endocrine response to a feed. Profound changes occur therefore in gut hormone physiology after birth and these changes may in part be due to enteral feeding itself. This data is of relevance to the design of optimal feeding regimes for high risk neonates.