The characteristics of the different populations of sensory nerve terminals that selectively contact pulmonary neuroepithelial bodies (NEBs) in rat lungs were investigated after chemical denervation with capsaicin and compared with control lungs. Vagal calbindin D28k and P2X(3) purinoceptor immunoreactive (IR) afferent nerve terminals contacting NEBs appeared to have their origin in the nodose ganglion. Thick CB/P2X(3)-IR nerve fibers were seen to be myelinated and to lose their myelin sheaths just before branching and protruding intraepithelially between the NEB cells. This vagal sensory component of the innervation of NEBs was not affected by capsaicin nor expressed capsaicin receptors (vanilloid receptor subtype 1). A second sensory nerve fiber population that selectively innervates pulmonary NEBs in the rat lung consists of thin unmyelinated nonvagal substance P/calcitonin gene-related peptide IR nerve fibers, contacting mainly the basal pole of pulmonary NEBs, and having their origin in dorsal root ganglia. In concordance with vanilloid receptor 1 expression on these nerve terminals, the spinal sensory substance P/calcitionin gene-related peptide-IR component of the innervation of NEBs was depleted by systemic capsaicin treatment. The complex sensory innervation pattern of pulmonary NEBs characterized in the present study strongly suggests that, physiologically, pulmonary NEBs represent a group of intraepithelial receptors that may be able to accommodate various local and central reflex actions, in relation to both chemo- and mechanosensory stimuli.