A recent electrophysiologic study has suggested the existence of 4 pacemakers in the colon which generate the electric waves that are responsible for the colonic motor activity. These pacemakers are located at the cecal pole, the cecocolonic junction, the mid third of the transverse colon and at the colosigmoid junction. We investigated the hypothesis that these pacemaker sites contain ICCs in great numbers and that the electric waves generated from these sites are transmitted by a chain of ICCs to the remaining colon. Specimens were taken from the 4 electrophysiologically defined pacemaker sites and the remaining colon of 24 cadavers. They were subjected to c-kit immunohistochemistry tests. Controls for antisera specificity consisted of tissue incubation with normal rabbit serum substituted for the primary antiserum. The morphometric study was performed by submitting the immunohistochemically-stained sections to image analysis in order to determine the area percent of immuno-reactivity in comparison to the total area of fields examined in the sections. Data obtained from the image analyzer were statistically analyzed. Immunohistochemical and morphometric studies have shown that the 4 electrophysiologically defined pacemaker sites contained a significantly higher proportion of ICCs than the remaining colon, the ICCs at these sites being multipolar and forming a network surrounded by a fibrous tissue wall. In the remaining colon, the ICCs were bipolar and arranged in a linear fashion. The study revealed the existence of a network of ICCs at the 4 pacemaker sites forming the 'pacemaker nodes' (PMNs). In the rest of the colon, a chain of ICCs extended in the colonic wall in a linear fashion forming the 'pacemaker bundles' (PMBs). We postulate that the colonic electric waves start at the PMNs and spread in the colon along the PMBs.