Distension induces secretion in the intact intestine, but the mechanism of this secretory process remains unresolved. We sought to characterize the effect of intraluminal pressures below 20 cmH2O on water and electrolyte movements in the rat ileum and the subsequent effects of two cholinergic antagonists, hexamethonium and atropine. An increase in intraluminal pressure from 3.0 to 12.5 cmH2O led to inhibition of net H2O and Na absorption and stimulation of HCO3 secretion. However, there was no significant change in Cl absorption. Secretion occurred in the absence of changes in tissue wet weight, intercellular fluid accumulation, villus tip erosions, or mannitol flux. Alterations in fluid and electrolyte absorption were prevented by the intra-arterial administration of hexamethonium (10 mg/kg). Atropine (0.5 mg/kg) had no effect. Our studies demonstrate that distension induces the secretion of Na and HCO3 by the intact ileum. This secretory process may represent a neurally rather than passively mediated mechanism.