Interstitial cells of Cajal (ICC) are morphologically and functionally intercalated between the elements of the enteric nervous system and the smooth muscle cells (SMCs) in the musculature of the digestive tract. Kit immunohistochemistry reliably identifies the location of these cells and provides information on changes in ICC distribution and density. Human oesophagus specimens (7 embryos, 23 fetuses at 7-27 weeks gestational age; both sexes) were exposed to Kit antibodies to determine ICC differentiation. Enteric plexuses were examined immunohistochemically by using anti-neuron-specific enolase, whereas the differentiation of SMCs was studied with antibodies against alpha-smooth-muscle actin and desmin. By week 7, c-kit-immunopositive cells were present along the entire oesophagus in the form of an uninterrupted layer around the myenteric plexus (MP) elements. From the beginning of the 3rd month, the number of ICC progressively decreased around the MP ganglia but increased within the muscle layers. Concomitantly, differences in the number and distribution of ICC were established in the various portions of the oesophagus: specifically, ICC were abundant in the lower portion, less numerous in the middle region and rare in the upper part. By the 5th month of development, the relationship as found in later developmental stages had been established: C-kit IR ICC were present within the circular muscle layer, within the longitudinal layer and in the connective septa surrounding the muscle bundles but were completely missing around the MP ganglia.