The measurement ex vivo of the resistance of low density lipoprotein (LDL) to oxidation promoted by copper is now being used in surveys of human populations at risk of developing atherosclerosis. However, it is not known whether a relationship between LDL oxidisability measured in this way and the development of atherosclerotic lesions exists. Using Watanabe rabbits as a model of the disease, we have found that dietary supplementation with the antioxidants, probucol and α-tocopherol, increased the resistance of LDL isolated from small volumes of plasma to oxidation. The antioxidant effects of probucol incorporated into LDL through dietary supplementation were greater than when incorporated ex vivo. When dietary supplementation was extended to a period of three months, the well established anti-atherosclerotic effects of probucol were confirmed and a highly significant relationship between the probucol content of the LDL particle and the extent of the atherosclerotic lesion in the aorta emerged. These results suggest that the assessment of the resistance of LDL isolated from plasma to oxidation promoted by copper may reflect the response of the arterial atherosclerotic process to antioxidant therapy.