The immediate effects of intravenous diltiazem effects and short-term (4 weeks) of the oral drug on systemic and regional hemodynamics, cardiac structure, and humoral responses were evaluated by previously reported methods in nine patients with mild-to-moderate essential hypertension and in one patient with primary aldosteronism. Diltiazem was first administered in three intravenous doses of 0.06, 0.06, and 0.12 mg/kg, respectively; patients were then treated for 4 weeks with daily doses ranging from 240 to 360 mg (average 300 mg). Intravenous diltiazem immediately reduced mean arterial pressure (from 115 ± 3 to 96 ± 3 mm Hg; p < .01) through a fall in total peripheral resistance index (from 37 ± 3 to 23 ± 2 U/M2; p < .01) that was associated with an increase in heart rate (from 66 ± 2 to 77 ± 3 beats/min; p < .01) and cardiac index (from 3.3 ± 0.3 to 4.3 ± 0.4 liters/min/m2; p < .01). These changes were not associated with changes in plasma levels of catecholamines or aldosterone or in plasma renin activity. After 4 weeks the significant decrease in mean arterial pressure persisted (104 ± 3 mm Hg; p < .01) and there were still no changes in the humoral substances or plasma volume. Renal blood flow index increased (from 368 + 52 to 462 + 57 ml/min/m2; p < .01) and renal vascular resistance index decreased (from 0.37 + 0.06 to 0.26 + 0.04 U/M2; p < .01), while splanchnic hemodynamics did not change. Left ventricular mass significantly decreased (from 242 ± 16 to 217 ± 14 g; p < .01). Thus, the fall in arterial pressure produced by diltiazem was associated with improved renal hemodynamics and reduced left ventricular mass without expansion of intravascular volume or alterations in circulating humoral substances.