Nutrients in the lumen of the small intestine are sensed by special cells in the epithelial lining. The ensuing neurohumoral reflexes affect gastrointestinal absorption/secretion, motility, and vascular perfusion. To study in vivo the effect of a monosaccharide (glucose) or polysaccharide (starch) present in the jejunum on glucose absorption from an adjacent part of the intestine and investigate the possible underlying mechanisms. Using the single pass intraluminal perfusion technique, a segment of jejunum (perfusion segment) was continuously perfused with 20mM glucose to determine glucose absorption. One hour later, a bolus of a saccharide was instilled in an isolated adjacent jejunal segment and the change in glucose absorption was monitored for a further 2h. The contribution of neural mechanisms in this process was investigated. Instillation of glucose (20mM or 40mM) in either distal or proximal jejunal pouch elicited immediate and sustained inhibition of glucose absorption (a decrease by 25%; P < 0.01) from the perfused jejunal segment. Comparable inhibition was obtained with instillation of other monosaccharides or starch in the jejunal pouch. This inhibition was abolished by adding tetrodotoxin to the pouch or to the perfused jejunal segment and also by pretreatment with sympathetic blockers (guanethidine or hexamethonium) and by chemical ablation of capsaicin-sensitive primary afferent fibers. Glucose absorption within the jejunum is auto-regulated through backward and forward mechanisms. This regulation is mediated by neural reflexes involving capsaicin-sensitive afferent and sympathetic efferent fibers. These reflexes might serve to protect against hyperglycemia.