Until recently, the embryological origin of the interstitial cells of Cajal (ICC) within the intestine was unclear. An origin from the neural crest or from the mesenchyme was considered possible because ICC possess some characteristics in common with neural crest-derived cells, and some characteristics in common with cells derived from the mesenchyme. Experiments in both mammalian and avian species, in which segments of embryonic gut were removed prior to the arrival of neural crest cells and grown in organ culture, have now shown that ICC do not arise from the neural crest. It appears that ICC and smooth muscle cells arise from common mesenchymal precursor cells. From mid-embryonic stages, ICC precursors express Kit, which is a receptor tyrosine kinase. Both ICC and many smooth muscle cell precursors initially express Kit, and then the cells destined to become smooth muscle cells down-regulate Kit and up-regulate the synthesis of myofilament proteins, whereas cells destined to differentiate into ICC maintain their expression of Kit. Adult mice with mutations that block the activity of Kit have disrupted arrays of ICC, whereas normal ICC are present until shortly after birth in such mice. It, therefore, appears that the Kit signalling pathway in not necessary for the embryonic development of ICC, but rather the post-natal proliferation of ICC.