To study regional metabolism and production of angiotensin II, we measured steady-state plasma levels of 125I-angiotensin I and II and endogenous angiotensin I and II in the aorta and the antecubital, femoral, renal, and hepatic veins during systemic infusion of 125I-angiotensin I or II. Extraction of arterially delivered angiotensin II ranged from 30-50% in the limbs to 80-100% in the renal and hepatomesenteric vascular beds both in essential hypertension (n = 13) and in unilateral renal artery stenosis (n = 7). Across the limbs, 20-30% of arterially delivered angiotensin I was converted to angiotensin II in both groups, and there was no arteriovenous gradient in endogenous angiotensin II. No conversion of arterially delivered angiotensin I was detected across the renal and hepatomesenteric beds, and there was net extraction of angiotensin II from the systemic circulation by these beds. Although regional production of angiotensin I at tissue sites made a significant contribution to its level in the veins, little of this locally produced angiotensin I reached the regional veins in the form of angiotensin II, even in the kidney with artery stenosis, where the venous levels of locally produced angiotensin I were particularly high. These results provide no evidence for a source of circulating angiotensin II other than blood-borne angiotensin I and illustrate the high degree of compartmentalization of angiotensin I and II production.