The rate of angiotensin generation with added renin in plasma from patients with benign essential hypertension has been shown to be higher than in plasma from norm ensive controls. An index of the angiotensin generation rate in relation to to al plasma renin substrate (PRS-r index) has been defined which allows for screening for "activated" plasma. In hypertensive subjects, this index was shown to be higher than that of the normotensive subjects (61 plus or minus 2.4 SE, and 45 plus or minus 5 SE). The index did not correlate with the absolute levels of blood pressure, 24-hour sodium excretion, or plasma renin activity in hypertensive subjects either during the control period or during acute alterations of blood pressure, but was shown to respond in a parallel fashion with chronically induced changes in blood pressure and circulating levels of angiotensin I. By the use of an isolated system of human renin and homologous renin substrate, we have demonstrated that plasma from hypertensive subjects contains a modifier of the renin reaction which increases both V-max and Km of the system, behaving as an uncompetitive activator. No significant change was noted with the addition of normal plasma to the same isolated system.