The immediate and short-term effects of lisinopril, a new converting enzyme inhibitor, on systemic and regional hemodynamics, cardiac structure and function and humoral indexes were evaluated in 10 patients with mild to moderate essential hypertension. A single oral dose of 5 mg lisinopril reduced mean arterial pressure from 118 to 104 mm Hg (p less than 0.01) and significantly increased (p less than 0.05) all load-dependent indexes of ventricular function (i.e., ejection fraction, velocity of circumferential fiber shortening and fractional fiber shortening rate). After 10 to 12 weeks of once-daily administration of lisinopril, mean arterial pressure remained reduced over a full 24-hour period (p less than 0.01), and was mediated through arteriolar dilation as expressed by the close correlation (r = 0.93, p less than 0.01) between changes in mean arterial pressure and changes in total peripheral resistance. Cardiac index decreased from 3.06 to 2.68 liters/min/m2 (p less than 0.01) without correlation to the decrease in arterial pressure (r = 0.06). Despite this reduction in cardiac index, renal blood flow increased from 861 to 1,053 ml/min (p less than 0.05) and renal vascular resistance decreased from 14 to 9 units (p less than 0.01). Left ventricular mass index decreased from 124 to 109 g/m2 (p less than 0.05), and left ventricular function remained unchanged. Thus, the decrease in arterial pressure produced by lisinopril was associated with improved renal hemodynamics and reduced left ventricular mass.