Our primary objectives are to evaluate the role of the vascular endothelium in the early development of the atherosclerotic lesion and elucidate the mechanism of contact inhibition and its role in dictating the physiological properties of a tissue such as the vascular endothelium. Since the vascular endothelial cells are the only cells which are continuously exposed to the full circulating concentrations of lipoproteins in vivo, we shall explore how contact inhibition can dictate the metabolic properties of a given tissue, like the vascular endothelium, which functions as a barrier with a selective permeability. We shall use the plasma lipoproteins LDL, VLDL, and HDL as probes. Our results with the vascular endothelium will be correlated both with those obtained with the corneal endothelium and those obtained with capillary endothelium of the fenestrated type, which we have recently developed in tissue culture. We will then analyze the basic mechanism through which the endothelium can acquire this property, an analysis which should shed some light upon the basic mechanism inducing/controlling contact inhibition.