The acute and chronic autonomic, systemic, and renal hemodynamic effects of trimazosin and placebo were studied in patients with uncomplicated essential hypertension of mild to moderate severity. In these studies, trimazosin effectively reduced arterial pressure through a decrease in peripheral vascular resistance. In the acute studies the cardiac output increased, whereas in the chronic studies it remained unchanged. Acutely, trimazosin selectively increased renal blood flow, which was out of proportion to the increase in cardiac output. No significant effects on autonomic function, metabolic function, or renin and aldosterone release were observed with trimazosin after acute or chronic administration. No tolerance to the action of the drug developed. No significant hemodynamic or metabolic changes were observed when compared with placebo either acutely or chronically. Our conclusions are as follows: (1) trimazosin is an effective and safe antihypertensive agent given in single daily doses; (2) it exerts its effects mainly through direct arteriolar dilatation and less through autonomic inhibition; (3) its antihypertensive effectiveness is not compromised by the development of tolerance; (4) it exerts a selective beneficial effect on renal circulation that is unrelated to systemic hemodynamic changes; and (5) these properties of trimazosin may make it a desirable drug for the treatment of hypertension complicated by renal failure.