Incomplete inhibition of endothelin-1-induced pressor effects by FR-139317, a novel, potent, ETA receptor antagonist, was observed in conscious, normotensive rats. Maximum inhibition by FR-139317 of the endothelin-1 pressor response (0.1, 0.3, 1.0 nmol/kg) was 49 +/- 7, 41 +/- 3, 62 +/- 5%, respectively. Two ETB-selective receptor ligands induced pressor responses in conscious rats. A portion of the endothelin-1 pressor response may be mediated by ETB receptors, and ETB-mediated vasoconstriction may contribute to incomplete inhibition of the pressor response to endothelin-1 by an ETA-selective receptor antagonist.