Recent evidence suggests that the expression of p75NTR and Trk neurotrophin receptors is essential for neuronal survival, not only during development, but also in adulthood. The aim of the present study was to investigate the cell localization and distribution of p75NTR and Trk receptors in the normal adult human enteric nervous system (ENS) using double-label immunohistochemistry. Immunoreactivity for p75NTR was observed in a few neurons, whereas Trk immunoreactivity was present in a higher percentage of neurons. Strong expression of both types of neurotrophin receptors was found in the enteric glia. In addition, Trk immunoreactivity was localized to nerve endings in the lamina propria, muscularis mucosa and along or between circular and longitudinal smooth muscle layers, as well as to the enteric epithelium. Furthermore, polynuclear cells, mast cells and folliculoreticular cells in the germinal layer of lymph nodes displayed p75NTR and/or Trk immunopositivity. Expression of neurotrophin receptors in an inflammatory tissue sample was much more intense compared with that of normal tissue samples. These results suggest that neurotrophin receptors, through interactions with neurotrophins, may play a critical role in functional integrity of the ENS during adulthood.