Chronic sustained hypertension leads to structural changes of the small and large arteries. These alterations consist of smooth-muscle hypertrophy, increased deposition of collagen, and “dilution” or destruction of elastin fibers. In addition, there may be no growth at all, but a “rearrangement” of vascular wall material termed “remodeling.” These changes serve to increase wall thickness and the media-to-lumen ratio and to decrease the external and internal diameter of the vessel—all of which contribute to increased systemic vascular resistance by the small arteries and increased impedance by the larger arteries. It has been suggested that these structural changes are an adaptive effort by the vessel to maintain a constancy of wall tension, but the end result is detrimental in that the effect is a further increase in systemic vascular resistance and blood-flow impedance, which lead to left ventricular hypertrophy and its consequences. The stimuli for these changes are stretch stimuli, mediated through stretch receptors on the arterial wall, and trophic stimuli mediated at the tissue level through the action of angiotensin II, aldosterone, and catecholamines. Angiotensin-converting enzyme inhibitors, especially those with effective tissue penetration, are ideal drugs to reverse these structural changes (“reverse remodeling”), decrease the systemic vascular resistance, and increase the vascular compliance. These agents exert their effects through suppression, at the tissue level, of angiotensin II, aldosterone, catecholamines, endothelins (ET₁, ET₃), and transforming growth factor-β₁ (TGF-β₁) and through an increase in local levels of kinins, prostaglandins, and nitric oxide, which have antigrowth effects. Although this is a class effect, it appears to be stronger with those angiotensin-converting enzyme inhibitors providing the greatest tissue penetration. (Am Heart J 1998;135:S21-S30.)