BACKGROUND: Lidocaine is often administered intravenously to suppress airway reflexes associated with tracheal intubation or tracheal suction. In addition, lidocaine is known to have airway relaxant effects through a direct relaxant mechanism on the smooth muscle. The presence of airway epithelium has been reported to reduce the sensitivity and maximum contractile response to histamine or acetylcholine(ACh). The purpose of this study was to determine whether the cumulative application of lidocaine may cause a concentration-dependent relaxation of the rat tracheal smooth muscle strips with intact or rubbed epithelium. METHODS: Using the rat tracheal smooth muscle strips, the effects of 10 6~3 10 3M of lidocaine pretreatment on isometric tension induced by 40 mM of K+ or 10 5M of ACh in presence or absence of adherent epithelium, and the influences of 10 6M of propranolol, 10 4M of L-NAME and 10 6M of atropine on relaxing response of lidocaine were studied. RESULTS: The tracheal smooth muscle concentration induced by K+ and ACh was similar magnitude both in presence or absence of adherent epithelium. The removal of epithelium did not affect the relaxant effect of lidocaine on the K+ and ACh-induced tracheal smooth muscle contraction. Lidocaine pretreatment reduced Ca2+-dependent contraction of the rat tracheal smooth muscle. Following pretreatment of the tracheal smooth muscle preparations respectively with propranolol, L-NAME and atropine the relaxing responses to lidocaine of tracheal smooth muscle were not depressed. CONCLUSIONS: These results suggest that the effect of the epithelium on lidocaine-induced relaxation of the tracheal smooth muscle is not significant and lidocaine may directly relax tracheal smooth muscle by the influences on the Ca2+ mobilization.