Both human and animal studies show that irritation of airway mucosa elicits a variety of reflex responses such as coughing, apnoea, and laryngeal closure. Most of the information concerning these reflex responses were obtained in anesthetized conditions with little applicability to awake conditions. Various aspects of cough and other reflexes on irritation of the airway mucosa are discussed. Studies on awake humans showed that stimulation of the laryngeal mucosa with a small amount of distilled water during wakefulness causes elicitation of the expiration reflex, cough reflex, and swallowing reflex while other types of responses are scarcely observed. In addition, the duration of these responses is remarkably short. In contrast, the same stimulation causes more variant, prolonged, and exaggerated responses during a light depth of anesthesia. An increase in depth of anesthesia abolishes expiratory efforts such as coughing and the expiration reflex whereas the apnoeic reflex and laryngeal closure reflex are resistant to the depressant effect of anesthesia. Also, the respiratory reflex responses to airway irritation varied, depending on the site of stimulation: both laryngeal and tracheal stimulation cause vigorous respiratory responses whereas bronchial stimulation causes little or no respiratory responses. These results indicate not only that the types and magnitude of reflex responses is greatly modified by the central nervous state but also that the site of stimulation is crucial for determining the pattern of respiratory responses elicited by airway stimulation in humans.