The clustering and concentration of autoantigens at the surface of apoptotic cells, in combination with the striking tolerance-inducing function of apoptotic cells, have focused attention on abnormalities in apoptotic cell execution and clearance as potential susceptibility and initiating factors in systemic autoimmunity. Structural changes that occur during cell death may influence the immunogenicity of self antigens. This article discusses the modifications that autoantigens undergo during cell death, identifies certain proimmune forms of apoptotic death in which autoantigen structure is frequently modified, and reviews the mechanisms through which such structural changes might lead to initiation of an autoimmune response.