Irritative toxic rhinitis is a nasal disorder induced by chemical compounds like ozone, formaldehyde, nickel, chrome, solvents and tobacco smoke. These noxious stimuli may have effects on the nasal innervation leading to a cascade of neuro-immune interactions and an augmentation of the symptoms. Here we examined changes in the neuropeptide content of mucosal parasympathetic, sympathetic and sensory nerves of patients with toxic rhinitis caused by chronic cigarette smoke exposure. Semiquantitative immunohistochemistry using antibodies against calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide tyrosine (NPY), and vasoactive intestinal peptide (VIP) was carried out on cryostat sections of human nasal mucosa obtained from normal subjects and patients with toxic rhinitis and revealed significant differences between both groups. Toxic rhinitis patients had significantly elevated expression scores for VIP (2.83 +/- 0.31 vs 1.27 +/- 0.47 control group) and NPY (3.17 +/- 0.31 vs 0.91 +/- 0.37 control group) revealing an increase of mediators in distinct subpopulations of airway nerves. In summary, the present studies indicate a differential participation of subclasses of mucosal nerves in the pathophysiology of toxic rhinitis. Airway innervation may have a major role in the pathophysiology of toxic rhinitis associated with chronic cigarette smoke exposure.