The interstitial cells of Cajal are proposed to have a role in the control of gut motility. The aim of this study was to establish the distribution of interstitial cells of Cajal in the wall of the normal human anorectum. Interstitial cells of Cajal express the proto-oncogene c-kit. Interstitial cells of Cajal were identified in the colon by immunohistochemical staining, using a rabbit polyclonal anti-c-kit antibody. Anorectal tissue was obtained at surgical resection for carcinoma of the colorectum. Density of interstitial cells of Cajal was graded. Statistical analysis was performed using chi2 tests. In the longitudinal and circular muscle layers of the rectum interstitial cells of Cajal were seen in the bulk of the muscle layer. In the intermuscular plane interstitial cells of Cajal encased the myenteric plexus. Interstitial cells of Cajal were found at the inner margin of the circular muscle and in association with neural elements of the submuscular plexus. Within the internal anal sphincter interstitial cells of Cajal were infrequently scattered among the muscle fibres. The density of interstitial cells of Cajal in the internal anal sphincter was significantly lower than that observed in the circular muscle layer of the rectum (P = 0.014). In conclusion, interstitial cells of Cajal are evenly distributed in the layers of the muscularis propria of the rectum, but have a lower density in the internal anal sphincter.