Capsaicin application to human nasal mucosa was found to induce painful sensation, sneezing, and nasal secretion. All of these factors exhibit desensitization upon repeated applications. The acute effects induced by capsaicin (300 micrograms/100 microliters) application to the nasal mucosa were studied in healthy volunteers and cluster headache patients. These effects were not different in both nostrils of cluster headache patients as well as in the single nostril of healthy controls. Likewise, the time course of desensitization to the painful sensation and nasal secretion induced by capsaicin applied for five consecutive days in control subjects was almost superimposable to those observed in the nasal mucosa of cluster headache patients. The number of spontaneously occurring attacks was significantly reduced in the 60 days after the end of capsaicin treatment. Whether the beneficial effect induced by capsaicin application to the nasal mucosa could be ascribed to a specific action on sensory neurons remains unknown.