It has been proposed that chemically reactive lipids released during lipid peroxidation convert low density lipoprotein (LDL), the major carrier of plasma cholesterol, to an abnormal form and that receptor-mediated clearance of this altered LDL produces cholesteryl ester deposition in macrophage-derived foam cells of atheroma. Immunocytochemical analyses now reveal the presence of protein modified by malondialdehyde, a peroxidative end product, which colocalizes with the extracellular deposition of apolipoprotein B-100 protein of LDL in atheroma from Watanabe heritable hyperlipidemic rabbits. These findings provide direct evidence for the existence in vivo of protein modified by a physiological product of lipid peroxidation within arterial lesions.