The distribution of neurotrophin receptors (p75, trkA-, trkB-, and trkC-receptor proteins) was studied by immunohistochemistry on sections of human gastrointestinal tract mucosa from esophagus through rectum. Moreover, chromogranin A (CgA) was studied in parallel to identify endocrine cells (EC). In all of the analyzed samples there was specific immunoreactivity (IR) for trkB-receptor protein in EC, the percentage of which varied between 26 +/- 0.6% for the duodenum and 78 +/- 3% for the sigmoid colon. EC displaying trkC-receptor protein IR were also encountered, in some cases, in EC of the gastric fundus (9%), duodenum (12%), jejune (23%), and colon (12%); trkA-receptor protein IR was occasionally present labelling EC in the jejune (52%), ileum (25%), and sigmoid colon (18%); finally, p75 was in 21% of EC exclusively in one case in the ileum. In addition to EC, IR for all assessed antigens was also present in the submucous blood vessels. Our results provide evidence for the occurrence of neurotrophin receptor proteins in nonneuronal tissues and suggest that neurotrophins, especially that binding trkB receptor proteins, can regulate a subpopulation of EC cells. However, whether EC expressing different trk receptor proteins represent neurochemical subtypes of EC, and whether the identified trk receptor proteins correspond to functional receptors, remain to be elucidated.