Aldosterone receptor blockade and thiazide therapy effectively lower blood pressure in geriatric hypertension. Their impact on sympathetic nervous system function has not been evaluated. In a double-blind, randomized study, 36 patients with stage 1 hypertension underwent 6 months of therapy with either aldosterone receptor blockade (spironolactone, n=19; 68±1 years) or hydrochlorothiazide (n=17; 68±2 years). Arterial blood pressure, [ ³ H]-norepinephrine (NE) kinetics (extravascular NE release rate), and α-adrenergic responsiveness (forearm vasoconstriction to graded intrabrachial artery NE infusions) were evaluated at baseline, after a 4-week antihypertensive medication withdrawal, and after spironolactone or hydrochlorothiazide treatment. Arterial blood pressure decreased significantly with both spironolactone (160±3 to 134±2 mm Hg; 77±2 to 68±2 mm Hg) and hydrochlorothiazide (161±4 to 145±4 mm Hg; 78±2 to 73±2 mm Hg) treatment. Sympathetic nervous system activity was significantly reduced after spironolactone (plasma NE: 378±40 to 335±20 pg/mL, P =0.04; [ ³ H]-NE release rate: 2.74±0.3 to 1.97±0.2 μg/min per meter squared, P =0.04) but not hydrochlorothiazide (plasma NE: 368±25 to 349±23 pg/mL, P =0.47; [ ³ H]-NE release rate: 2.63±0.4 to 2.11±0.2 mg/min per meter squared, P =0.21). α-Adrenergic responsiveness was unchanged with either drug treatment. These findings demonstrate a beneficial effect of aldosterone receptor blockade on reducing sympathetic nervous system activity and blood pressure in hypertensive older patients.