We have previously observed that after addition of exogenous renin, the rate of angiotensin I generation is faster in plasma of hypertensive patients and patients with renal disease than in plasma of normotensive subjects. We have demonstrated that this increased reactivity of renin may be related to the deficiency of circulating renin inhibitors. The purpose of this project is to identify inhibitors of renin in plasma and to determine if the different enzymatic activities of renin in hypertensive and uremic plasma are related to different concentrations of circulating renin inhibitors. We have previously demonstrated that crude neutral lipids inhibit the in vitro renin reaction and that free fatty acids inhibit renin both in vitro and in vivo. We are currently evaluating the possibility that phospholipids also inhibit renin. These lipid fractions, and the fatty acid composition of each lipid fraction will be studied in clinical situations where different enzymatic activities of renin have already been demonstrated.