The potential of angiotensin-converting enzyme (ACE) inhibitors to protect the heart is a topic that has emerged recently as matter of scientific discussion. Experimental and clinical studies have shown the beneficial effects of ACE inhibitors on the metabolism, function, and structure of healthy and damaged hearts and these studies support the concept of both primary and secondary "cardioprotection" with these drugs. More recently, the prevention of atherosclerotic lesions has been demonstrated in animal models, extending the concept to a more general definition of "cardiovascular" protection with ACE inhibitors involving both the heart and the vessels. The potential role of ACE inhibitors on the primary prevention of atherosclerotic disease in humans is currently evaluated in PHYLLIS (Plaque HYpertension Lipid Lowering Italian Study), a multicenter clinical trial in which fosinopril sodium, a new ACE inhibitor, is administered to hypertensive patients with at least one uncomplicated carotid artery lesion. The primary aim of the study is to evaluate the effect of the drug on the long-term (3 years) progression of carotid artery atherosclerosis, noninvasively detected by B-mode ultrasound imaging. In addition to studies on primary prevention, some large clinical trials have been conducted to establish the role of ACE inhibitors on secondary prevention, in particular in patients with acute myocardial infarction (MI). The beneficial effect of these drugs is well established when administered in the subacute phase of acute MI.(ABSTRACT TRUNCATED AT 250 WORDS)