Surgical specimens from various parts of the human intestinal tract as well as suction biopsy specimens, including mucosa and submucosa of the rectum, were fixed in formalin and embedded in paraffin by routine procedures. The distribution of immunoreactive areas indicating the presence of neuron-specific enolase (NSE) was then determined by using a sheep anti-human-NSE antiserum prepared in our laboratory. The immunocytochemical method revealed, in distinct contrast to other tissue components, the cell bodies of ganglion cells in the submucosa (Meissner's plexus) and in the muscle layers (Auerbach's plexus). The nerve bundles of the submucosa, of the muscle layers, and of the subserosal connective tissue were also stained, whereas the thin nerve processes of the mucosa were identified only rarely. The smooth muscle cells were stained weakly, but this reaction did not interfere with the identification of the neurons and their processes. Immunocytochemical demonstration of NSE is obviously a valuable additional method for visualization of the intrinsic intestinal innervation. It might well be that this technique will be of advantage in the diagnosis of pathologic processes, such as those occurring in Hirschsprung's disease and allied conditions.