To determine the response of the preterm infant's intestine to entire feedings at different postnatal ages, we recorded results of manometry of the gastroduodenum and determined fasting plasma concentrations of gastrin, gastric inhibitory peptide, neurotensin, and peptide YY three times in each of two groups: 27 preterm infants were randomly assigned to receive hypocaloric enteral nutrition on postnatal days 3 to 5 (early feeding) or on days 10 to 14 (late feeding). Initial observations (study 1) were performed by the fifth postnatal day; study 2 was performed on days 10 to 14, and study 3 on days 24 to 28. Early-fed infants received hypocaloric feedings immediately after study 1; late-fed infants did not receive enteral feedings until the completion of study 2. Although motor activity and fasting gastrointestinal peptide concentrations did not differ between groups at study 1, at study 2 early-fed infants had significantly more mature motor patterns than did babies not being fed. Early-fed infants also had significantly higher plasma concentrations of gastrin and gastric inhibitory peptide than did late-fed infants; neurotensin and peptide YY values were similar in both groups. By the time of study 3, when late-fed infants had also received enteral feedings, gut development was not different in the two groups. However, early-fed infants were able to tolerate full oral nutrition sooner, had fewer days of feeding intolerance, and had shorter hospital stays. Thus the provision of early hypocaloric nutrition was associated with earlier nutrition of preterm infants' intestinal function and resulted in improved feeding tolerance. These findings support the use of early feedings in preterm infants.