Endothelin-1 (ET-1), one of the most potent constrictors of airway smooth muscles, is reported to act on such inflammatory cells as mast cells and release several chemical mediators. We observed a transient relaxation response to ET-1 after an anaphylactic constriction of guinea pig tracheal smooth muscle. The guinea pig was actively sensitized with ovalbumin, and the tracheal strip was challenged with ovalbumin in vitro. ET-1 induced a transient relaxation followed by a constriction of the tracheal strip. The potency of the relaxation induced by 10(-9) M of ET-1 was 16.0 +/- 1.3%, compared to the response to isoproterenol (2 x 10(-5) M), and the duration of the relaxation was 7.2 +/- 0.7 minutes. Indomethacin (10(-6) M) had no effect on the response, indicated that prostaglandins have no relation. Mechanical denudation of the tracheal epithelium did not reduce the relaxation, but rather augmented it. These results indicate that ET-1 induces a relaxation, associated with a relaxation factor from non-epithelial tissue.