The endothelium controls the tone of the underlying vascular smooth muscle cells by secreting vasodilator [prostacyclin, nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF)] and vasoconstrictor (superoxide anions, endoperoxides, thromboxane A2, endothelin) substances. The vasodilator substances also contribute to the antithrombogenicity of the normal endothelium and inhibit cellular growth. The release of endothelium-derived NO and EDHF is augmented by increases in shear stress (flow-dependent vasodilatation) and a number of neurohumoral substances. Among the latter, endogenous bradykinin plays a key role, in particular as a mediator of flowdependent responses. In coronary vascular disease, the ability of the endothelium to secrete vasodilator substances is reduced, while its propensity to release endothelium-derived contracting factors is increased. In particular, the reduced release of NO in response to aggregating platelets, thrombin, and circulating catecholamines favors the occurrence of thrombosis and vasospasm, and plays a key role in the initiation of the atherosclerotic process. From the therapeutic point of view, the best available way to enhance the release of endothelium-derived NO and EDHF is to inhibit angiotensin-converting enzyme (ACE). This protects endogenous bradykinin from breakdown and prolongs its action on endothelial receptors. In addition, certain, but not all, ACE inhibitors interact directly with the kinin receptors on the endothelial cells...