Endothelin-1 (ET-1) is a potent endogenous vasoactive peptide whose role in regulation of vascular tone is unclear. BQ123 is a recently described ETA receptor antagonist which may be useful in further investigation of the physiologic and pathophysiologic significance of ET-1. To test its efficacy in the pulmonary circulation, the vascular response to exogenous ET-1 with and without BQ123 was assessed in rat pulmonary artery (PA) rings and salt-perfused lungs. In both main and distal (250-350 microns ID) PA rings, BQ123 significantly attenuated ET-1-induced contractility, but was more effective in the larger vessels. Likewise, BQ123 significantly blunted ET-1-induced vasoconstriction in perfused lungs by > 80%. In addition, it had no effect on ET-3-mediated or U46619-mediated vasoconstriction, nor did it influence ET-1-induced vasodilation. Development of ET-1-associated hydrostatic edema was also unaffected by BQ123. We conclude that BQ123 effectively attenuates ET-1-induced vasoconstriction in both PA rings and in isolated perfused lungs. The absence of effect of BQ123 on ET-3 vasoconstriction, ET-1 vasodilation, or ET-1- and ET-3-induced hydrostatic edema formation suggests that these processes may be transduced through a non-ETA receptor.