The respiratory and olfactory mucosae of rats and mice were examined at ultrastructural levels for the presence of intraepithelial nerve endings. Immunocytochemical studies utilizing antisera directed against substance P and calcitonin gene-related peptide (CGRP) revealed numerous intraepithelial peptide-immunoreactive fibers near the basal region of the epithelium. Occasional transepithelial fibers were observed to extend outward to nearly reach the epithelial surface. In no cases, however, did the transepithelial fibers reach the surface, but instead, stopped at the line of tight junctions approximately 1 micron from the surface. No specialized contacts between the nerve fibers and the epithelial cells were observed. The transepithelial fibers provide a possible anatomical substrate for the sensitivity of the trigeminal nerve to many air-borne chemical stimuli. That potential chemical stimuli must traverse the tight-junctional barrier may explain why lipid solubility is related to effectiveness for trigeminal stimuli.