Associations between coronary events and plasma renin activity, and between coronary risk reduction and angiotensin-converting enzyme (ACE) inhibitors, are now well recognized. Improvement in endothelial function may explain, in part, some of the effects of ACE inhibitors in reducing the rates of adverse cardiovascular outcomes observed in clinical trials. ACE inhibitors have been shown to restore the endothelium-mediated vascular relaxation response in animal models of severe atherosclerosis. Clinical trials are now under way to examine the effect of ACE inhibitors on surrogate outcomes that allow assessment of endothelial function in the progression of carotid and coronary atherosclerosis. The recently completed Trial on Reversing ENdothelial Dysfunction (TREND) demonstrated improved coronary endothelium-dependent vasomotor function after 6 months of treatment with quinapril. In addition, quinapril treatment was associated with a trend toward an increase in microvascular blood flow response. Other studies in progress will assess the effect of ACE inhibitors on clinical coronary risk and plaque progression.