Diagnosing Hirschprung's disease is one of the clinical challenges of this disorder. In the stomach and the intestines, Cathepsin D was readily detected in cytoplasm of the rat gastric and in intestinal ganglion cells of the autonomic nervous system. The objectives of the present study were to examine cathepsin D expression in ganglion cells of the submucosal and myenteric plexuses of the intestine of children and to determine the utility of immunohistochemical staining of cathepsin D for detection of immature ganglion cells. Paraffin blocks of 35 intestinal segments were reviewed for immunohistochemical staining with polyclonal antibody to cathepsin D and hematoxylineosin stainings from the compatible specimens. There were 9 aganglionic segments and 9 ganglionic segments of neonates with Hirschsprung's disease, 8 intestinal segments with non-Hirschsprung's disease in neonates and 9 intestinal segments with non-Hirschsprung's disease infants over the age of 10 months. All ganglion cells showed intense granular cytoplasmic reactivity for cathepsin D regardless of maturity and all aganglionic segments had no expression for cathepsin D in the submucosal and myenteric plexuses of the intestine. However, histiocytes within the laminar propria and submucosa stained positively for cathepsin D. In conclusion, intestinal ganglion cells in children have reactivity for cathepsin D, threrfore immunohistochemical staining for cathepsin D can be used for identification of ganglion cells in neonates.