Established essential hypertension is characterised haemodynamically by a normal cardiac output and elevated total peripheral resistance. As hypertensive cardiovascular disease progresses, and the patient grows older, cardiac output falls and total peripheral resistance is further elevated. The activity of the renin-angiotensin-aldosterone (RAA) system declines throughout life and reaches its lowest levels in the elderly, unless there is congestive heart failure. In long-standing hypertension, target organ disease such as left ventricular hypertrophy, nephrosclerosis and cerebrovascular damage is commonly observed. Rational antihypertensive therapy should therefore aim to lower total peripheral resistance, spare cardiac output, and maintain or improve blood flow to target organs. ACE inhibitors lower arterial pressure by decreasing total peripheral resistance, they maintain or improve cardiac contractility, promote regression of left ventricular hypertrophy, and increase renal blood flow. Lisinopril is a novel ACE inhibitor that does not contain a sulphydryl group. It is not a prodrug and thus does not require bioactivation by the liver. Lisinopril has a long duration of action, allowing it to be used as a single daily dose in the treatment of hypertension. Preliminary studies from our laboratory indicate that lisinopril reduces cardiac output and preload to the left ventricle. Lisinopril also reduces left ventricular hypertrophy and lowers renal vascular resistance, thereby increasing renal blood flow. In patients with mild to moderate hypertension, lisinopril is more effective than hydrochlorothiazide in reducing both systolic and diastolic blood pressure, and is at least as effective as atenolol or metoprolol in reducing diastolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)