Epithelial endocrine cells containing 5-hydroxytryptamine, substance P, somatostatin, enteroglucagon and vasoactive intestinal polypeptide-immunoreactivity were localized by immunocytochemistry in the mucosa of normal appendices, ileum and proximal colon, and in neurogenic appendicopathy. In neurogenic appendicopathy a large number of proliferating nerves were visualized independently of neurotransmitters by immunostaining for neuron-specific enolase. A large number of nerve fibers were shown to contain substance P-immunoreactivity and to be of intrinsic origin. Stromal endocrine cells containing 5-hydroxytryptamine, somatostatin- and possibly substance P-immunoreactivity, were observed in substantial numbers in neurogenic appendicopathy. Substance P may be involved as a neurotransmitter and/or as a paracrine/endocrine peptide in the pathogenesis of spastic contractions and abnormal peristalsis of the appendix, which are characteristic of neurogenic appendicopathy. Stromal endocrine cells may be considered to be the origin of certain carcinoids in the appendix.