The possible involvement of immunological mechanisms in the pathogenesis of atherosclerosis has been suggested intermittently since the early 1970s. Both humoral and cellular mechanisms have been proposed to participate in the onset and/or progression of atheromatous lesions, but the theories postulating the involvement of autoantibodies and immune complexes have met with considerable experimental support. Modified lipoproteins, particularly different forms of oxidized LDL, have been reported to elicit humoral immune responses in both experimental animals and humans. Oxidized LDL has been demonstrated in atheromatous lesions, anti-oxidized LDL antibodies have been detected in circulation and in atheromatous plaques, and immune complexes formed with LDL and anti-LDL have been isolated from the serum of patients with manifestations of atherosclerosis. In addition, in vitro-formed LDL-IC and IC isolated from patients have been demonstrated to cause intracellular accumulation of cholesteryl esters (CE) in human macrophages and fibroblasts. The accumulation of CE in macrophages exposed to LDL-IC is unique to this type of IC and is associated with a paradoxical overexpression of the native LDL receptor and with increase synthesis and release of interleukin 1 and TNF-alpha. The release of these cytokines in the subendothelial space may have a significant role in promoting the interaction of endothelial cells with mononuclear cells, causing endothelial cell damage directly or indirectly, and also in inducing smooth muscle cell proliferation. Thus, several lines of evidence suggest that humoral autoimmunity may play a significant role in the pathogenesis of atherosclerosis.