Neurogenic appendicopathy is a frequent (17.8%), non-purulent form of appendicitis. Light microscopy enabled differentiation between an intramucosal variant, a type with central neuroma and neuromuscular proliferations in the submucosa. All nerves within the gut wall were visualized independently of neurotransmitters by immunostaining for neuron-specific enolase. Proliferation of nerve fibres with substance P- and VIP-immunoreactivity was observed in the intramucosal variant and in central neuroma. Moreover, an increase was found in stromal endocrine cells with 5-hydroxy-tryptamine-, somatostatin- and substance P-immunoreactivity. These endocrine stroma cells are considered to be the site of origin of appendix carcinoids. We, therefore, suggest that appendix carcinoids originate in-frequently multicentric-foci of small endocrine cell groups localized within proliferating nerve fibres in the subepithelial stroma, independent of the epithelial layer.