BACKGROUND The functions of the gut are modulated by the autonomic nervous system and gut peptides, such as somatostatin and cholecystokinin, which have opposite functions. This study reports plasma somatostatin and cholecystokinin levels in response to feeding in preterm infants. METHODS In 76 infants--gestational age 23 to 36 weeks, birth weight 460 to 2867 g--blood samples were taken on day 1 before the first meal in life, and 30 minutes after the end of the meal. Samples were again taken on days 3 and 4. The infants were fed human milk by nasogastric tube, by breast, or by bottle. In 10 additional infants, (gestational age 27-36 weeks) who were studied at a median postnatal age of 15 days, the response of the peptides to breast-feeding was compared with that of tube-feeding. Plasma somatostatin and cholecystokinin were analyzed by specific radioimmunoassays. RESULTS On day 1, the median plasma somatostatin level increased after feeding in small-for-gestational-age infants but not in appropriate-for-gestational-age infants. On days 3 and 4, the somatostatin level decreased in infants with a gestational age of 32 weeks or more. On day 1, plasma cholecystokinin levels increased in infants with a gestational age of 32 weeks or more: The response was more pronounced in small-for-gestational-age infants. On days 3 and 4, plasma cholecystokinin levels increased only in breast-feeding infants. In the 10 infants fed by breast and by tube, plasma cholecystokinin levels increased after breast-feeding and tended to increase after tube-feeding. The plasma somatostatin levels were unaffected after feeding. CONCLUSIONS Plasma somatostatin and cholecystokinin increased after feeding in small-for-gestational-age infants on day 1. On days 3 and 4, the responses to feeding seemed to be dependent on the infant's gestational age. Breast-feeding enhanced the release of cholecystokinin but not that of somatostatin.