We examined the role of interstitial cells of Cajal (ICC) in the ascending and descending neural reflexes in the ileal segments prepared from wild type mice and c-kit mutant W/WV mice. Localized distension of the ileal segments from wild type mice with a small balloon caused contraction or relaxation of the circular muscle on the oral or anal side of the distended region, respectively. However, these intestinal reflexes were not induced in the ileal segments from the mutant mice. In the small strips that include the step of the pathways from efferent motor neurons to smooth muscle cells, nerve stimulation induced contraction of circular muscle in the absence of atropine and relaxation in the presence of atropine. The extent of nerve stimulation-induced contractions and relaxations of the ileal circular muscle were similar in wild type and W/WV mice. The responsiveness of ileal circular muscle to exogenously added acetylcholine and Nor-1, a nitric oxide donor, was also unaffected in the mutant ileum. Since previous immunohistochemical study had revealed selective loss of ICC within the myenteric plexus (ICC-MY) in the mutant ileum, it was concluded that ICC-MY have an essential role in ascending and descending neural pathways in the mouse ileum.