Background/Aims: The interstitial cells of Cajal (ICC) are located within and around the digestive tract’s muscle layers. They function as intestinal muscle pacemakers and aid in the modification of enteric neurotransmission. The appendix’s unique position requires an appropriate contraction pattern of its muscular wall to adequately evacuate its contents. We investigated the development and distribution of nervous structures and ICC in the human fetal appendix. Methods: Specimens were exposed to anti-c-kit (CD117) antibodies to investigate ICC differentiation. Enteric plexuses were examined using antineuron-specific enolase, and the differentiation of smooth muscle cells was studied with anti-desmin antibodies. Results: During weeks 13-14, numerous myenteric plexus ganglia form an almost uninterrupted sequence throughout the body and apex of the appendix. Fewer ganglia were present at the submucosal border of the circular muscle layer and within this layer. A large number of ganglia appear within the circular and longitudinal muscle layers in a later fetal period. The first ICC subtypes noted were of the myenteric plexus and the submucous plexus. In the later fetal period, the number of intramuscular ICC markedly rises, and this subtype becomes predominant. Conclusions The ICC and nervous structure distribution in the human fetal appendix are significantly different from all other parts of the small and large intestine. The organization of ICC and the enteric nervous system provides the basis for the specific contraction pattern of the muscular wall of the appendix.