Recently, it has been suggested that oxidized low density lipoprotein (LDL) plays an important role in atherogenesis by facilitating the accumulation of lipids in macrophages. In vitro studies from our laboratory have shown that oxidized LDL is recognized not only by a specific receptor, but also by a receptor which recognizes both oxidized LDL and acetyl LDL. Probucol, originally developed as an antioxidant, prevents the oxidative modification of LDL in vitro. Our recent studies show that probucol prevents the progression of atherosclerosis in homozygous WHHL rabbits in vivo without any changes in plasma LDL cholesterol levels. These results strongly suggest that oxidative modification of LDL could occur in vivo and probucol could slow the progression of atherosclerosis, especially the foam cell-rich fatty streak lesions, without changing plasma cholesterol levels.