A therosclerotic lesions develop over decades at specific sites in the human arterial system. These lesions have diverse and complex morphological characteristics, but are frequently characterised by excessive deposition of cholesterol. Many studies have focused on the role of cholesterol delivering lipoproteins, particularly low density lipoproteins (LDL), as pivotal factors in the evolution of atherosclerotic lesions. However, no atherogenie mechanisms have been ascribed to native LDL. To explain this apparent paradox, a hypothesis has evolved that the atherogenicity of LDL is related to oxidative modification of lipoprotein particles in arterial tissue. Oxidised LDL have a broad spectrum of biochemical properties that may contribute to the development of atherosclerotic lesions. Much of the earlier work on oxidative modifications of LDL has been reviewed by Steinberg and colleagues.’2 Several lines of evidence support the occurrence of oxidation in atherosclerotic lesions. Lipoproteins isolated from both experimental and human atherosclerotic lesions have physical and biochemical properties consistent with those of oxidised particles. Also, a number of antibodies generated against oxidation adducts have been used to immunolocalise these epitopes in atherosclerotic lesions. Furthermore, specific chemical oxidation products have been detected in atherosclerotic tissue. While the presence of oxidative processes in atherosclerotic lesions has been established, mechanisms of oxidation have not been defined. Free transition metal ions, such as copper and iron, are a requirement for oxidative modification of lipoproteins by most cultured cells, although the relevance of this requirement to the in vivo environment is unknown. Enzymes that potentially mediate cellular oxidative modification of LDL include 15-lipoxygenase and myeloperoxidase. The manner in which oxidised lipoproteins are metabolised in vivo has also not been clarified. Recent studies have defined multiple receptors on macrophages that recognise oxidised LDL. The discovery of multiple lipoprotein receptor classes provides further possible mechanisms by which foam cell formation may be regulated. Detection of oxidation products in atherosclerotic lesions has provoked many studies on the potential effects of antioxidants on the disease process. Previously, the major focus of antiatherogenic regimens has been on hypocholesterolaemic agents. The rationale for this approach partly stemmed from the prominence of plasma lipoprotein derived cholesterol in atherosclerotic lesions. A role for cholesterol in atherogenesis was further implied by the appearance of premature atherosclerosis in subjects with familial hypercholesterolaemia. Therefore, it has been assumed that the reduction of plasma cholesterol concentration will reduce the extent of the disease. Indeed, findings of various studies indicate that the reduction of plasma cholesterol concentrations with diet and drug therapy reduces the incidence and severity of atherosclerotic diseases, 3-6 although the benefits of such interventions remain controversial.’’More recently, another strategy has emerged that focuses on oxidative stress and its consequences with regard to lipoprotein metabolism. This review will briefly summarise the potential involvement of oxidation in the development of atherosclerosis, then assess the evidence that antioxidants possess antiatherogenic properties.