BACKGROUND The ingestion of a meal increases water and electrolyte absorption from the jejunoileum. Recent observations have implicated Na(+)-glucose cotransport as a primary mediator of meal-stimulated jejunal absorption. The current experiments tested the hypothesis that Na+/H+ exchange is a major mediator of basal and meal-stimulated ileal absorption. METHODS Absorption studies (n = 36) were performed on dogs with 25 cm ileal Thiry-Vella fistulas. Six groups were studied for 4 hours. Luminal perfusion with 14C-polyethylene glycol was used to calculate absorption of water, sodium, chloride, and glucose. A 480 kcal canine meal was ingested in groups 2, 3, 5, and 6. Luminal amiloride (1 mmol/L) was used to inhibit Na+/H+ exchange in groups 1, 3, 4, and 6. To assess Na(+)-glucose cotransport the luminal perfusate contained either 10 mmol/L glucose (groups 1 through 3) or 10 mmol/L mannitol, a nontransported hexose (groups 4 through 6). RESULTS Ileal absorption increased significantly in response to a meal in the presence of both glucose (group 2) and mannitol (group 5). Amiloride caused a significant reduction in basal and postmeal water and electrolyte absorption, largely independent of the glucose-mannitol content of the luminal perfusate. Mannitol significantly reduced basal absorption of water and electrolytes. CONCLUSIONS These data indicate that both Na+/H+ exchange and Na(+)-glucose cotransport contribute to basal ileal water and electrolyte absorption, whereas Na+/H+ exchange appears to be the primary mediator of meal-stimulated ileal absorption. Na+/H+ exchange appears to play a major role in the physiologic regulation of postprandial ileal absorption.