Hyperreflectoric rhinitis is related to an unspecific hyperreactivity probably caused by chemical irritants. As a major modulatory role may be attributed to the mucosal innervation, the present study was carried out to examine possible changes in the nasal mucosa innervation. Immunohistochemistry for the neuropeptides vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP) and neuropeptide tyrosine (NPY) revealed abundant staining of nerve fibers. Neuropeptide-contents in mucosal nerves was then quantitatively assessed and significant increases were found for SP (3.00 ± 0.37 vs. 1.64 ± 0.34 control group staining intensity) and VIP (2.33 ± 0.42 vs. 0.82 ± 0.33). In conclusion, these findings demonstrated differences in human nasal mucosa innervation between nonrhinitic and hyperreflectoric rhinitic subjects and provide evidence for a modulatory participation of neuropeptide-specific subpopulations of nerve fibers in hyperreflectoric rhinitis.