Despite numerous investigations on the enteric nervous system, the knowledge about the mucosal innervation of the human rectum and colon is very shallow and mainly based on ultrastructural studies. We performed an enzyme (NADH-Ach) and immunohistochemical (NF, synaptophysin, anti-Leu-19) study on cryostat sections of the human rectal mucosa in order to study the possible additional characteristics of the mucosal innervation in depth. Enzyme histochemistry reveals positively staining fibers in the muscularis mucosae. Staining with antibodies against neurofilaments and synaptophysin reveals positively staining fibers in the lamina propria and muscularis mucosae. The latter staining is comparable with the findings obtained with anti-Leu-19. The monoclonal antibody anti-Leu-19 is characterized by a nerve-like staining in the mucosa revealed by nerve-like fibers from the plexus submucosus internus (Meissner) penetrating the muscularis mucosae, and creating a real plexus of fine twisted fibers in the lamina propria, around the crypts and underneath the epithelium. The distribution of the mucosal nerve-like pattern in the areas with mucosa-associated lymphoid follicles differs from the pattern observed in the lamina propria in between. Since the monoclonal antibody anti-Leu-19 and the monoclonal antibody NKH1a show a great similarity, we were interested also in the possible relation between the nerve like mucosal staining pattern and the lymphocytic population. Comparing the distribution pattern of anti-Leu-19 with other lymphocytic markers, there was an apparent similarity with the distribution of the T-helper subgroup. Our data indicate that the monoclonal antibody anti-Leu-19 shows a nerve-like staining pattern in the mucosa.