Normal rabbits were injected intravenously with horseradish peroxidase (HRP) and 125I-labeled human low density lipoprotein (LDL), and the aortas were perfusion-fixed. Subsequent visualization of HRP in the aortas was produced by reaction of the tissue with diaminobenzidine and hydrogen peroxide. The luminal surface of the aortas showed many small punctate foci of brown reaction product to the HRP, which represented penetration of the HRP into the vessel wall. The foci were scattered over the luminal surface, and most of the focal areas were less than 1 mm in diameter. The concentration of LDL was up to 47 times greater in these focal areas than in surrounding noncolored regions not showing increased permeability to HRP. Small circumscribed foci of heightened permeability to LDL may predispose to the local accumulation of lipid and ultimately to the formation of atherosclerotic plaques.