Decreased splanchnic vascular response to exogenous angiotensin-I1 (A-11) infusion in portal hypertension has recently been documented. A-II receptor density and binding affinity in the mesenteric artery, portal vein, and adrenal gland of normal and portal hypertensive rabbits were studied. Portal hypertension was induced by partial portal vein ligation 3 weeks before study. There were no significant differences in serum concentrations of sodium, potassium, A-11, serum osmolality, or hematocrit between normal and portal hypertensive rabbits. The portal hypertensive portal vein exhibited a 60% fall in A-I1 receptor number from 65.1 t 0.3 fmoY mg in normal to 27.0 ? 8 fmoYmg (P < .05) in portal hypertension. A significant decrease in receptor number occurred in the portal hypertensive mesenteric artery, 224 f 39 fmoYmg compared with 345 ? 45 fmoYmg in normal rabbits, and in the adrenal cortex 6.8 t 1.3 pmoY mg compared with 12.1 ? 2.5 pmoYmg in normal controls (P < .05). No significant difference in A-I1 receptor aβ¬finity was observed in tissues studied between normal and portal hypertensive rabbits. Autoradiographic study on A-I1 receptors was consistent with data from membrane binding assays. Receptor subtype analysis showed exclusive type I receptor binding in the mesenteric artery and portal vein. We conclude there is a global reduction in the A-11 receptor number in portal hypertension that may mediate much of the decreased response to A-I1 seen in this disorder. This loss of the A-I1 receptor may partially explain hemodynamic derangements peculiar to portal hypertension. (HEPATOLOGY 1995; 22559-564.) Pressor hyporesponsiveness to angiotensin-I1 (A-11) in the splanchnic circulation has recently been shown to occur in a model of prehepatic portal hypertension (PHT) (PHT secondary to partial portal vein ligation Abbreviations: A-11, angiotensin-11; PHT, portal hypertensive; NL, normal; PRA, plasma renin activity; PBS, phosphate-buffered saline; EGTA, ethylene glycol-bis-(8-aminoethyl)N,N,N,N tetraacetic.