CP-804-S is a substituted phenylbutylamine, known to lower arterial pressure in hypertensive animal models. In a double-blind, crossover study, 12 patients with essential hypertension receiving a constant sodium intake received placebo and CP-804-S, 150 mg daily. Standing (-5.5/-6.0 mm Hg) and supine (-8.5/-7.5 mm Hg) blood pressures and standing (-7.0 beats/min) and supine (-7.5 beats/min) pulse rates were significantly reduced by CP-804-S. Plasma renin activity (-0.41 ng/ml/hr) and plasma angiotensin I (-47 pg/ml) and angiotensin II (-3.0 pg/ml) levels decreased significantly. No significant changes were observed in plasma aldosterone or in the urinary excretion of aldosterone, kallikrein, and prostaglandin E2, F2 alpha, and F alpha metabolite.