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Objective To investigate the distribution of nitric oxide synthase (NOS), nerve growth factor receptor (NGFR) and interstitial cells of Caial (ICCs) in Hirschsprungs disease (HD). Methods The distribution of NOS,NGFR and ICCs was studied by using NADPH diaphoruse histochemistry, immanohistochemistry with a monoclonal antibody to human NGFR and the specific polycloual antibody against c-kit in 8 normal controls and 10 cases of HD.Results NOS and NGFR were abundantly present in the myenteric plexus and in the nerve fibers of musculature. ICCs were intensively distributed in the surface of circular musculature and around the myenteric plexus to form a network in normal control colon. In contrast, NOS and NGFR were scarce or absent in the myenteric plexus and in the nerve fibers of musculature, while the hypertrophic nerve trunks were NGFR positive, ICCs were scarcely distributed and the network was disrupted in the aganglionic colon in HD. Conclusion These findings suggest the Involvement of NOS,NGFR and ICCs in the patbophysiology of HD.