Interstitial cells of Cajal (ICC) are thought to play an important role in the control of gut motility. The regional and transmural distribution of ICC in the normal human alimentary tract was investigated using c-kit immunohistochemistry. ICC were detected in the myenteric plexus layer of the esophagus, corpus, pylorus, small intestine, colon and rectum. Intramuscular ICC could be demonstrated in the esophagus, fundus, corpus, pylorus, colon, rectum and anal canal. ICC at the deep muscular plexus were found only in the small intestine. In the pylorus, colon and rectum, ICC were also found at the submucosal border of the circular muscle layer. In addition, scattered ICC were noticed among the smooth muscle fibers of the gall bladder wall. Computer-aided image analysis for quantitative morphometric study of ICC was also performed. The results of such technique verified the histological findings as proved by statistical analysis. In addition, five specimens of gastrointestinal stromal tumors (GISTs) were obtained and they showed positive c-kit immunostaining supporting the suggestion that ICC may be precursors of GISTs.