This report describes the molecular pharmacological properties of LR-B/081 (methyl 2-[[4-butyl-2-methyl-6-oxo-5-[[2'-(1H-tetrazol-5- yl) [1,1'-biphenyl]-4-yl]methyl]-1 (6H)-pyrimidinyl]methyl]- 3-thiophenecarboxilate), a novel non-peptide angiotensin II receptor antagonist. This compound potently displaced [3H]angiotensin II from angiotensin AT1 (Ki = 1.4 nM, rat adrenal cortex), but not from angiotensin AT2 (Ki > 1 microM, bovine cerebellar cortex) receptors and did not show affinity for other receptor systems (Ki > 10 microM). In saturation studies, LR-B/081 both increased KD and decreased Bmax values in a dose-dependent fashion. The rate of dissociation of [3H]angiotenin II from angiotensin AT1 receptors was not affected by the presence of 1 microM LR-B/081 and the association rate of [3H]angiotensin II was not decreased by the presence of 1 or 30 nM LR-B/081, indicating that the Bmax reduction was not due to an allosteric interaction or to a delay in reaching the steady-state conditions. These data underline the complexity of the antagonistic nature of LR-B/081, presenting features of both competitive and noncompetitive antagonism.