Trichloroethylene (TCE) and perchloroethylene (PERC) have been reported to induce respiratory complications such as airway hyperactivity and asthma. The present study was designed to investigate their influence on smooth muscle contraction and epithelial release of prostanoids in swine trachea. Results showed that TCE and PERC exposure did not alter the basal tone of tracheal smooth muscle. However, TCE and PERC concentration-dependently increased both ACh-induced and high K+-induced muscle contraction. In addition to potentiation of muscle contractile responses evoked by acetylcholine or histamine, pretreatment of smooth muscle with PERC at higher concentration significantly suppressed the relaxant activity of beta-adrenergic agonists. The epithelial prostaglandin (PG)E2, but not PGD2, release from tracheal epithelium was significantly increased by TCE and PERC. In addition, the acetylcholinesterse (AChE) activity of tracheal epithelia was reduced by TCE and PERC. In conclusion, our results suggest that the enhancement of spasmogen-evoked muscle contractile responses and epithelial PGE2 secretion, as well as reduction of epithelial AChE activity, may participate in airway impairment and hyperresponsiveness after TCE and PERC exposure.