Distension-evoked reflex rectal (R-R) contractions and internal anal sphincter (R-IAS) relaxations can be generated in guinea pigs through an extrinsic sacral excitatory neural pathway (pelvic nerves) as well as intrinsic cholinergic excitatory and nitrergic inhibitory pathways. The aim of the present study was to create intrinsic R-R and R-IAS reflex models by destruction of the lumbar and sacral cords (PITH) and evaluate whether the prokinetic benzamide, mosapride, a 5-HT4 receptor agonist, enhances these reflexes. The mechanical activities of the R-R and R-IAS were recorded in the anesthetized guinea pig on 2- 9th day after PITH. Although the basal rectal pressure at distension after PITH was significantly lower than control, the reflex indexes of R-R contractions and synchronous R-IAS relaxations were unchanged between 4-9 days after PITH. The frequency of spontaneous rectal and IAS motility were also unchanged. Immunohistochemical studies revealed that the distribution of myenteric and intramuscular interstitial cells of Cajal were not altered after PITH. Mosapride (0.1-1.0 mg/kg IV) dose-dependently increased both intrinsic R-R (maximum: 1.82) and R-IAS reflex indexes (maximum: 2.76) from control (1.0) 6-9 days after PITH. The 5-HT₄ receptor antagonist, GR 113808 1.0 mg/kg IV decreased the R-R and R-IAS reflex indexes by approximately 50% and antagonized the effect of mosapride 1.0 mg/kg IV. The present results indicate that mosapride moderately enhanced intrinsic R-R and R-IAS reflexes functionally compensated after deprivation of extrinsic nerves, mediated through endogenously active, intrinsic 5-HT₄ receptors.