To better understand the role of cnteric nerves in the regulation of colonic ion transport in neonates, we examined the effects of endogenous and exogenous neurcltransmitters on ion transport across distal colonic tissues of piglets. Tissues were obtained from full-term fetuses; newborns; suckling piglets killed 1 d, 5 d, and 14 d after birth; and 21-d-old piglets that had been weaned for 2 d. Colonic tissues were stripped of external muscle layers and mounted in Ussing flux chambers. Short-circuit current (Isc), a measure of active ion transport, and transmural potential difference were lowest in fetal colons and increased during postnatal development. Tissue conductance remained constant throughout development until d 14 and then rose sharply after weaning. Blockade of enteric neural transmission with tetrodotoxin reduced basal Isc compared with control tissues in fetal, newborn, and 1-d-old piglets but had no effect in older animals. The Na+-channel blocker amiloride had no effect on basal Isc in fetal tissues but significantly reduced Isc in all other groups, with the effect increasing with age. Isc responses to electrical field stimulation of cnteric neurons were similar in fetal throughThe extrinsic and intrinsic nerves that innervate the gastrointestinal tract are important modulators of intestinal ion transport (1, 2). Neuromodulation of intestinal transport is a key w a y in which the gut processes sensory information from luminal and systemic stimuli and initiates appropriate effector mechanisms that maintain the proper consistency and composition of luminal contents (1). Although a number of studies have now identified neural pathways and specific neurotransmitters that regulate transport function, virtually all of these reports have focused o n adult animals o r humans o r at least young animals that have already been weaned. Consequently, apart from the study by Carey and Cooke (3) in 14-d-old piglets and then increased after weaning. Increases in Isc after serosal additions of carbachol (10 KM), serotonin (10 pM), or norepinephrine (10 FM) in fetal and newborn piglets were as great or greater than in the older piglets. For serotonin and norepinephrine, Isc responses rose sharply immediately after weaning. In 1-d-old piglets, Isc responses to all stimuli wcre reduced significantly by removal of C I ions from the bathing solutions. At all ages Isc responses wcre inhibited by bumctanide (10 FM) but were not affected by amiloride. These results demonstrate that colonic CI secretion evoked by endogenous or exogenous addition of neurotransmitters is well developed at an early age in piglets. The aim of the present study w a s t o examine the effects of endogenous and exogenous neurotransmitters o n colonic ion transport during postnatal development in piglets. Although the role of hormonal signals, particularly aldosterone, in mediating developmental changes in colonic ion transport has been studied in several species (4-lo), the effect of enteric neurotransmitters o n colonic