BACKGROUND: Asthma can be described as the hypersensitivity of the airway to various stimuli. Injury to tracheal epithelial cells could be the reason for tracheal hypersensitivity in asthma or upper respiratory infection. This study is based on the hypothesis that the dysfunction of the airway in asthma is caused by epithelial cell injury. METHODS: After isolating guinea-pig tracheal preparations, in order to examine the role of airway epithelium in response to smooth muscle, we measured the contractile responses to acetylcholine, carbachol, and histamine on the isolated epithelium-denuded or epithelium-intact guinea-pig tracheal preparations. When tracheal tones were stabilized, each contractile agent was added cumulatively to the organ baths to obtain concentration-response curves, and ED50 and ED95 were calculated. RESULTS: In both groups, tracheal tones increased in response to contractile agents, in concentration- dependent manners. In comparing both groups, the contractility of denuded trachea was increased by 10 7 and 10 6 M in acetylcholine, and by 10 6 M in histamine significantly. In denuded trachea, ED50 and ED95 increased significantly in response to both acetylcholine and histamine. However, they did not increase in carbachol. CONCLUSIONS: The removal of the epithelium increased the contractile responses to acetylcholine and histamine.