Local and systemic capsaicin pretreatment as well cryosurgery induced a long-lasting loss of sensory substance P-immunoreactive nerves in the guinea-pig nasal mucosa. In addition, cryosurgery caused a loss of noradrenergic sympathetic nerves, sclerosis of blood vessels, epithelial damage and fibrosis of the mucosa. The sneezing response to local application of capsaicin'''but not that to nicotine'''was reduced or abolished by capsaicin pretreatment and cryosurgery, while the response to tactile stimulation was unaffected. These effects were long-lasting and still present 2 months after treatment. Local capsaicin pretreatment of the nasal mucosa had no effects on the substance P levels or the Evans Blue extravasation response to i.v. capsaicin in the ureter, indicating that this treatment has no systemic effects on other afferent SP-neurons. It is suggested that local capsaicin pretreatment is a more selective and less traumatic method than cryosurgery to induce a long-lasting desensitization of the nasal mucosa to chemical irritants in hyperreactive disorders of the nose.