The immediate and short-term cardiovascular effects of oral isradipine therapy were evaluated in 11 patients with mild to moderate systemic hypertension. Isradipine, 5 mg administered orally, induced a significant reduction in arterial pressure from 165 ± 6/88 ± 3 mm Hg to 140 ± 5/76 ± 2 mm Hg (p < 0.001) within 2.5 hours by a decrease in total peripheral resistance associated with an increase in heart rate and cardiac output. Contrary to the acute effect, oral therapy with isradipine for 3 months reduced arterial pressure through a decrease in total peripheral resistance but without causing an increase in heart rate or cardiac output or activation of the sympathetic nervous system. Isradipine slightly reduced left ventricular mass and improved cardiac systolic function and left ventricular filling. Renal blood flow increased, and renal vascular resistance (p < 0.01) and total blood volume (p < 0.002) decreased without a change in either sodium excretion or body weight. Thus, isradipine, when given for 3 months, decreased arterial pressure by reducing total peripheral resistance without activation of reflexive mechanisms. Its favorable effects on systemic hemodynamics, total blood volume, renal blood flow, and cardiac structure and function suggest isradipine to be an excellent choice for antihypertensive therapy.