Damage to or dysfunction of respiratory epithelial cells may contribute to the etiology of bronchial hyperreactivity in asthma and airway infection. This brief overview summarizes the data, which suggest that release of relaxing factor(s) from epithelial cells may contribute to the regulation of bronchomotor tone. Reduced release of this epithelium-derived relaxing factor(s) may help to explain in part bronchial hyperreactivity secondary to epithelial damage.