We studied the effect of indomethacin, a cyclooxygenase inhibitor, on bradykinin-induced responses in the intact and denuded epithelium of the isolated tracheal smooth muscle in guinea pigs. Epithelium removal alone did not alter the responsiveness to bradykinin. Indomethacin (2.8 microM) enhanced the sensitivity to bradykinin of both intact and denuded preparations. This finding suggests that the tracheal epithelial may have no protective effect on the contractile responses induced by bradykinin. This may be due to the presence of high amounts of bradykinin-inactivating enzymes in the tracheal smooth muscle. Indomethacin-medicated potentiation caused by bradykinin in epithelium intact and denuded preparations may be an indication of removal of the bronchodilator prostaglandin biosynthesis. The significance of these findings is discussed.