Atherosclerosis is accompanied by a local immune response in plaque, but its role in the pathogenesis of the disease is still unclear. Although we might expect that an (auto)immune response would be an aggravating factor, some of its consequences could be protective. Studies of human plaques and of lesion formation in apo E-0 mice show that CD4+ T cells and macrophages form an inflammatory infiltrate. Both cell types are activated and secrete proinflammatory cytokines. CD4+ cells respond immunospecifically to oxidized LDL, suggesting that oxidation induces antigenic epitopes on LDL and converts it to an autoantigen. The pathophysiological consequences of this response are probably mediated largely via cytokine secretion and cell-cell contacts. Th1 cytokines dominate and may promote vascular inflammation; this is enhanced by the increased capacity for activation of NF-kappaB in intimal smooth muscle cells. The net effect of such activity appears to be proatherogenic, as can be deduced by cell transfer into immunodeficient apoE-0 x SCID mice. These data emphasize the importance of inflammation and immune responses in the pathogenesis of atherosclerosis.