Rationale: chronic exposure of human isolated bronchi to ₂-adrenergic agonists, especially fenoterol, potentiates smooth-muscle contraction in response to endothelin-1, a peptide implicated in chronic inflammatory airway diseases. Objective: to determine whether endothelin-1 receptors ETA and ETB are involved in fenoterol enhancement. Methods: twenty-two human bronchi were sensitized to endothelin-1 by prolonged incubation with 0.1 µM fenoterol (15 hours, 21°C). Measurements and Main Results: removing the epithelium after fenoterol incubation limited the maximal contraction (0.10 ± 0.36 g without epithelium vs. 1.18 ± 0.22 with, n = 8, p = 0.04). After 15 hours incubation, 14 and 8 paired rings were fixed, respectively for immunolabeling of bronchial ETA and ETB receptors, and to determine the mRNA expression levels using real-time quantitative reverse transcription polymerase chain reaction. ETA- and ETB-receptor mRNA expressions were 1.27 ± 0.14-fold (not significant) and 2.24 ± 0.28-fold (p < 0.01) higher, respectively, in fenoterol-treated bronchi than in paired controls. Fenoterol incubation significantly increased epithelial ETA- and ETB-receptor labeling intensity scores (p = 0.001 and p = 0.002, respectively, vs. controls), and enhanced the diffuse localization of ETA receptors on the epithelial cells (p = 0.002 vs. controls) but did not change the ETB-receptor immunolabeling intensity on airway smooth muscle. Conclusions: fenoterol-induced sensitization of human isolated bronchi involves epithelial ETA and ETB receptors, which suggests perturbation of the epithelial regulation of airway smooth muscle contraction in response to endothelin-1.