Atherosclerosis in animals and humans is associated with an unresponsiveness of arteries and arterioles to endothelium-dependent vasodilators--agents acting on smooth muscle indirectly by stimulating the release from endothelial cells of a vasodilator principle (endothelium-derived relaxing factor). Altered vasomotor regulation in atherosclerosis could partly reflect an injurious action of abnormal lipoproteins on endothelium. Recently, 'cell-modified' or 'oxidized' low-density lipoprotein (EC-LDL) has received increasing attention because of its potential cytotoxic and atherogenic properties. We report here that arteries exposed to EC-LDL in vitro show an endothelium-dependent vasoregulatory impairment closely resembling that of atherosclerotic arteries. Our results indicate that transfer of lysolecithin from EC-LDL to endothelial membranes produces a selective unresponsiveness to receptor-regulated endothelium-dependent vasodilators.