Intestinal neuronal dysplasia (IND) is a malformation of the enteric plexus that clinically resembles Hirschsprung's disease (HD). In HD, the aganglionic bowel is characterized by the presence of hypertrophic nerve trunks and increased numbers of adrenergic and cholinergic nerve fibers, whereas IND type B (IND-B) is characterized by dysplasia of parasympathetic nerves, hyperganglionosis, and giant ganglia. The aims of this study were to investigate the relationship between the distribution of mast cells (MC) and abnormal neuronal innervation and the impact of abnormal neuronal innervation on colonic epithelial differentiation in relation to the typical innervation abnormalities seen in HD and IND. Full-thickness rectal-biopsy or resected surgical specimens from 15 patients (7 HD, 4 IND, 4 control) were examined by conventional hematoxylin-eosin, periodic acid-Schiff Alcian blue (PAS-AB), toluidine blue staining. The aganglionic and IND-B segments had larger numbers of MC in all layers than the ganglionic and control segments. There was a close relationship between the hypertrophic nerve fibers and the distribution of the MC. In contrast to the aganglionic segments, the mucin composition of the IND-B segments was normal. This finding suggests that innervation anomalies do not reflect epithelial differentiation to the same extent.