Not only the plasma cholesterol level, but also postsecretory modifications of lipoproteins appear to be of influence in atherogenesis. Evidence that several forms of modification, especially oxidation, occur in vivo is rapidly accumulating, although their clinical relevance remains uncertain. Modification of lipoproteins has been demonstrated in persons with such well-known risk factors of premature atherosclerosis as smoking, diabetes mellitus and hyperlipidaemia. Because there is a relation between the amount of natural antioxidants in the plasma and the risk of atherosclerosis, and because exogenous antioxidants appear to retard atherosclerosis without influencing the plasma cholesterol level, antioxidants may prove to be of use in the prevention of atherosclerosis. There are strong indications for a role of the immune system in atherogenesis. Modified lipoproteins are highly immunogenic and stimulate immunocompetent cells to secrete vasoactive factors and cytokines. From animal studies it appears that pro- and antioxidative conditions can modulate these processes. It is concluded that additional research on the relation between lipoprotein modification and the immune system, and on the possible beneficial effects of antioxidants in atherogenesis is warranted, not only to elucidate further the mechanism of atherosclerosis, but also to develop new approaches to the prevention of atherosclerosis.