Because duodenal motor activity differs between preterm and term infants during fasting, this study evaluated the responses of motor activity and peptide release in response to feeding. In the first study, fasting concentrations of gastrin, gastric inhibitory peptide, neurotensin, and peptide YY (PYY) were determined in 53 preterm and 20 term infants. Plasma concentrations of gastrin and neurotensin were significantly lower in preterm infants than in healthy adults reported previously by our lab (p less than 0.01). Plasma concentration of gastric inhibitory peptide and PYY were higher than in healthy adults (p less than 0.01). Gastrin concentrations in preterm and term infants varied directly with gestational age (p less than 0.005); PYY varied inversely with gestational age (p less than 0.005). In a secondary study, intestinal manometry was recorded and serial peptide concentrations were determined in 43 preterm babies who were given their first enteral feeding intraduodenally with formula or sterile water. Although none of the four peptide plasma concentrations changed in response to feeding with water, plasma concentrations of gastric inhibitory peptide, neurotensin, and PYY significantly increased with formula feedings (p less than 0.05 or less). In addition, plasma gastrin increased significantly in seven infants fed milk compared with eight fed water by orogastric tube (p less than 0.01). In contrast to the peptide response to feeding, motor activity changed in response to feeding with either water or milk; motility indices increased and periods of motor quiescence decreased significantly during feeding as compared with fasting (p less than 0.02). Responses of both motor activity and peptides to feeding were time related.(ABSTRACT TRUNCATED AT 250 WORDS)