The neurochemical features of the nitrergic and peptidergic innervation of the porcine esophagus were investigated by means of immunohistochemical methods combined with vagotomy. Neuronal cell bodies in both the submucosal and the myenteric plexus (MP) were detected immunoreactivities for nNOS, VIP, GAL, NPY, PACAP, L-ENK, SP, 5-HT and CB, while CGRP- and SOM-immunoreactive (ir) somata were not encountered. In addition, nNOS- and CB-ir myenteric neurons constituted the separate enteric subpopulations.Double immunostainings with a general neuronal marker (PGP9.5 ) and the specific markers, such as nNOS, VIP and SP revealed (1)nNOS-ir myenteric neurons in the porcine esophagus accounted for a higher percentage (63 % ) of all esophageal intrinsic PGP9.5-ir neurons in comparison of VIP-ir (36%) and SP-ir populations (28%); (2) An increasing rostrocaudal gradient in the number of myenteric neurons per ganglion as well as a significantly higher number of enteric ganglia within both plexuses in the abdominal segment; ( 3 ) The densest nerve fibers within the esophageal musculature were VIP-/GAL-/NPY-ir, some of which also co-expressed nNOS and/or PACAP immunoreactivity. The number of L-ENK- and/or SP-ir fibers was significantly higher in lamina muscularis mucosae ( LMM ) than in tunica muscularis externa (TME). In contrast to reports in other species, CGRP-ir fibers within the porcine esophagus constituted a very limited population and were extrinsic; (4) Vagotomy experiments revealed an obvious decrease of PACAP-and 5-HT-ir nerve fibers within the MP,suggesting that these fibers originate from the vagal nerve, while these nNOS- and/or VIP-/GAL-/NPY-ir fibers innervating both the TME and the LMM did not appear to be significantly affected by the vagotomy procedure, possibly being the intrinsic origin.