The circular muscle layer of the human caecum and ascending colon is clearly subdivided into two portions: an outer one which includes the bulk of the circular muscle layer, and an inner one made up of only six to eight rows of cells. In the right transverse colon no demarcation can be observed, but a difference exists between the innermost and the outermost cells, since those of the two innermost rows possess some peculiarities with regard to the sarcoplasmic reticulum, glycogen particles, caveolae, and intercellular junctions. In the left part of the colon, the circular muscle layer is also divided into two portions. In fact, the innermost smooth muscle cells still possess peculiar morphologies, progressively increase in number, and become separate from each other making up a superficial muscle network. A fibrous lamella, along and inside which a ganglionated nerve plexus runs, is strictly apposed to the submucosal border of the circular muscle layer of the entire colonic length. A second nerve plexus runs between the two portions of the circular muscle layer. Both these plexuses are accompanied by interstitial cells of Cajal in the right colon only. The peculiar organization of the entire submucosal border of the human colonic circular muscle layer distinguishes it from other parts of the gut and probably represents a structural basis for control of human colonic motility. The presence of putative pacemaker cells (interstitial cells and peculiar smooth muscle cells) indicates that the inner border of human colonic circular muscle layer possesses pacemaking activities. Moreover, the interstitial cell--smooth muscle cell ratio differs depending on the colonic level; two main regions can be identified: the right and the left colon. Consequently, we might expect regional variation in pacemaking.