The role of aldosterone in low renin hypertension remains controversial. Patients with classical primary aldosteronism are now being identified by failure to suppress plasma aldosterone concentration (PA) normally during saline infusion, and only a small percentage of low renin patients have classical primary aldosteronism. Previous studies have shown that aldosterone secretion and excretion done under random or regular dietary salt conditions is normal in the vast majority of cases of essential hypertension. However, in low-renin patients with normal saline suppression of PA, we have noted failure of aldosterone suppression in response to sodium loading (high salt diet plus Florinef) in a large percentage of patients (11 of 30 overall and 9 of 23 in blacks). Development of new RIA's for urinary tetrahydroaldosterone and plasma tetrahydroaldosterone glucuronide has facilitated these studies and allowed much more accurate quantitation of aldosterone regulation. An adrenal abnormality which causes excess aldosterone secretion in response to multiple stimuli and failure of feedback suppression with sodium loading is suspected. This postulate will be tested by determining changes in PA in these patients vs normal subjects vs low renin patients with normal aldosterone regulation and normal renin patients in response to infusion of ACTH, angiotensin, and potassium. In addition, studies with metoclopramide and bromocriptine will allow testing of the possibility that these patients have defective dopaminergic inhibition of aldosterone secretion. Determination of plasma tetrahydroaldosterone glucuronide during saline infusion and validation of an outpatient protocol for Florinef suppression should allow simpler identification of these patients. Preliminary evidence suggests that this type of aldosterone-mediated hypertension may be more common in blacks, and so comparison with white hypertensive patients will be done. In addition, preliminary experience suggests that patients with more severe hypertension will achieve satisfactory blood pressure control with high dose metolazone plus spironolactone therapy. These studies should clarify the hypertensive mechanism in many low renin patients through specific evaluation of this distinct subgroup.