Trimazosin was given for periods of at least 6 mo to 25 patients with mild to moderate essential hypertension. In doses of 300 to 900 mg dialy trimazosin alone led to blood pressure control (supine diastolic blood pressure less than 90 mm Hg with a fall of at least 10 mm Hg) in 16 patients (64%). Despite the decrements in blood pressure there were no changes in body weight or creatinine clearance. There was also no changes in plasma renin activity or urinary aldosterone excretion rate. Although patients with high control renin values appeared to have greater blood pressure decreases than those with low renin values, responsiveness to treatment was not associated with consistent effects of trimazosin on the renin-angiotensin system. Trimazosin induced a small decrease in plasma total cholesterol concentration. In seven patients whose blood pressures were not controlled by trimazosin alone, the addition of polythiazide led to decreased blood pressure and in five control of pressure was achieved. Thus, trimazosin is an effective antihypertensive when given by itself or in combination with a diuretic. Its mechanism of action has not been established, but its ability to induce vasodilation without concomitant sodium retention or stimulation of the renin axis may be an important factor in its effectiveness.