Low density lipoprotein (LDL) undergoes oxidative modification in vivo, which is a key step in the development of atherosclerosis. Oxidative modification of LDL generates conjugates between fragments of oxidized fatty acids and apolipoprotein B, and is recognized by macrophage receptors. Three lines of evidence support this: (1) antibodies against oxidized LDL, malondialdehyde-lysine, or 4-hydroxynonenal-lysine recognize materials in atherosclerotic lesions of LDL receptor-deficient rabbits; (2) LDL extracted from these lesions is recognized by an antiserum against malondialdehyde-conjugated LDL; (3) autoantibodies against malondialdehyde-LDL are present in rabbit and human sera. Oxidative modification of LDL enhances its atherogenicity. Monocyte-derived macrophages cannot take up native LDL rapidly enough to cause lipid loading, but oxidative modification converts LDL into a form recognized by the macrophage acetyl-LDL receptor. Oxidative modification of LDL is accompanied by degradation of its polyunsaturated fatty acids, generating shorter chain fragments that become covalently linked to apolipoprotein B. These modified apolipoproteins are recognized by the acetyl-LDL receptor. The study used immunochemical methods to show that LDL undergoes oxidative modification in vivo. LDL was isolated from atherosclerotic lesions and found to contain apolipoprotein B and fragments reactive with antibodies against MDA-lysine and 4-HNE-lysine. Autoantibodies against MDA-LDL were found in rabbit and human sera, indicating that oxidized LDL may be a source of autoantibodies. The findings suggest that LDL undergoes oxidative modification in vivo, accumulates in aortic lesions, and may be a source of autoantibody production. While these findings do not establish a pathogenetic role for oxidized LDL, they support its presence in vivo. Antioxidant therapy slows the progression of atherosclerosis, suggesting that oxidized LDL may play a pathogenetic role. Autoantibodies against MDA-LDL may contribute to this process by forming immune complexes that are taken up by macrophages.Low density lipoprotein (LDL) undergoes oxidative modification in vivo, which is a key step in the development of atherosclerosis. Oxidative modification of LDL generates conjugates between fragments of oxidized fatty acids and apolipoprotein B, and is recognized by macrophage receptors. Three lines of evidence support this: (1) antibodies against oxidized LDL, malondialdehyde-lysine, or 4-hydroxynonenal-lysine recognize materials in atherosclerotic lesions of LDL receptor-deficient rabbits; (2) LDL extracted from these lesions is recognized by an antiserum against malondialdehyde-conjugated LDL; (3) autoantibodies against malondialdehyde-LDL are present in rabbit and human sera. Oxidative modification of LDL enhances its atherogenicity. Monocyte-derived macrophages cannot take up native LDL rapidly enough to cause lipid loading, but oxidative modification converts LDL into a form recognized by the macrophage acetyl-LDL receptor. Oxidative modification of LDL is accompanied by degradation of its polyunsaturated fatty acids, generating shorter chain fragments that become covalently linked to apolipoprotein B. These modified apolipoproteins are recognized by the acetyl-LDL receptor. The study used immunochemical methods to show that LDL undergoes oxidative modification in vivo. LDL was isolated from atherosclerotic lesions and found to contain apolipoprotein B and fragments reactive with antibodies against MDA-lysine and 4-HNE-lysine. Autoantibodies against MDA-LDL were found in rabbit and human sera, indicating that oxidized LDL may be a source of autoantibodies. The findings suggest that LDL undergoes oxidative modification in vivo, accumulates in aortic lesions, and may be a source of autoantibody production. While these findings do not establish a pathogenetic role for oxidized LDL, they support its presence in vivo. Antioxidant therapy slows the progression of atherosclerosis, suggesting that oxidized LDL may play a pathogenetic role. Autoantibodies against MDA-LDL may contribute to this process by forming immune complexes that are taken up by macrophages.