We studied the pharmacologic properties of LR-B/057, a novel nonpeptide angiotensin II (AII) receptor antagonist. The compound potently displaced [3H]AII from AT1 but not from AT2 receptors in rat adrenal cortex (Ki 3 nM), but did not modify the dissociation rate of the radioligand from the receptors. Both its affinity and the nature of its interaction with AT1 receptors (saturation studies) were markedly affected by the presence of bovine serum albumin (BSA) in the binding assay. In rabbit aorta, LR-B/057 caused nonparallel shifts to the right of the dose-response curve to AII and decreased the maximal response (pKB 9.6). Oral (p.o.) administration of LR-B/057 to conscious rats dose-dependently antagonized the pressor response to AII. LR-B/057 administered either intravenously (i.v.) or p.o. to conscious renal hypertensive rats produced a powerful dose-dependent antihypertensive effect. These results show that LR-B/057 is a potent and selective antagonist at AT1 receptors and has p.o. bioavailability.