Slow transit constipation (STC) is a colonic motility disorder that is characterized by measurably delayed movement of stools through the colon. The pathophysiology of STC is unclear and both the interstitial cells of Cajal (ICC) and cells of the enteric nervous system are believed to play an important role. The aim of this study was to compare the number and distribution of ICC and cells of the enteric nervous system in patients with a control group by means of immunohistochemistry. Formalin-fixed paraffin-embedded colonic sections were obtained from 15 patients, aged between 23 and 52 (mean age=37 y), who underwent colectomy for STC. Forty-five cases of normal colon from age and sex-matched nonobstructive colorectal cancer patients were selected as controls. By using c-kit (CD117) and PGP 9.5 immunohistochemical studies, ICC and enteric neurofilaments were demonstrated, respectively. The number of cells were counted under 40 x high-power field (HPF) in 3 layers of the colonic muscularis propria, that is, the inner circular muscle layer, the myenteric plexus, and the outer longitudinal muscle layer in both test and control groups. The mean number of ICC and enteric neurofilaments were significantly reduced in all 3 layers of the muscularis propria from STC patients compared with controls. This reduction was most significant in the inner circular muscle layer (P<0.0001). A cutoff value of 7 ICC per HPF in the inner circular muscle layer can be used as a further confirmation to the clinical diagnosis of STC in resected specimens.