The concentrations of plasma proteins of different molecular weights were measured in layers across the human aortic wall. On a volumetric basis the concentration of low density lipoprotein (LDL) in inner intima, adjacent to the endothelium, was almost twice the concentration in the patient's plasma. With the exception of transferrin, which behaved anomalously, the concentration of each protein was a linear function of is plasma concentration and molecular weight, so that the relative retention of albumin was only 15% of LDL retention and its concentration in inner intima less than one-quarter of the plasma concentration. Between the inner (luminal) and outer layers of intima the concentration of all proteins decreased by about 40%. In aortas in which the internal elastic lamina (IEL) appeared to be intact it provided an almost total barrier to LDL, but for smaller proteins the concentrations in the layer immediately outside it were inversely related to molecular weight; the concentration of LDL was only 0.3% of the intimal concentration whereas albumin was 26% of the intimal concentration. However, in aortas in which the IEL appeared morphologically frayed, fragmented or discontinuous there was an 80% increase in albumin, and a 25-fold increase in LDL in this layer. The differential barrier functions of endothelium and IEL produce bizarrely different macromolecular environments for smooth muscle cells in intima and media.