The cardiovascular effects of intravenous verapamil and 3 months of oral administration of a slow-release form of verapamil (verapamil-SR) were studied in 10 patients with mild-to-moderate essential hypertension. Intravenous verapamil reduced arterial pressure by 15% (p less than .01) through a fall in total peripheral resistance of 29% (p less than .01); provoked a reflexive rise in heart rate (by 19%, p less than .02), cardiac output (by 74%, p less than .01), and plasma catecholamines; and shifted intravascular volume toward the cardiopulmonary circulation indicating peripheral venoconstriction. Quite in contrast to the immediate effects of the intravenous drug, oral therapy with verapamil-SR for 2 to 3 months lowered arterial pressure effectively (by 15%, p less than .01) by inducing vasodilation of 15% (p less than .02), but without causing reflex tachycardia, activation of the sympathetic-adrenergic or renin-angiotensin systems, or volume expansion. Oral therapy with verapamil-SR preserved systemic and renal blood flow and slightly reduced cardiac mass (by 6%, p less than .05) and renal vascular resistance (by 25%, p less than .05). Whereas intravenous verapamil tended to depress myocardial contractility, oral verapamil-SR did not at all affect myocardial contractility or left ventricular function. These cardiovascular effects make verapamil-SR an excellent agent for long-term antihypertensive therapy.