Evidence is lacking that antibodies (Ab) to endothelial cells (AECA) are pathogenic. They are frequently associated with antiphospholipid Ab (aPL), binding to complexes of phosphatidylserine (PS) with beta2GPI. Recent studies have, however, kindled a new debate on their pathogenicity of AECA. A group is responsible for PS reaching the surface of a cell, a feature of commitment to apoptosis. Defective clearance by macrophages of AECA-induced apoptotic cells might display beta2GPI on their surface, and challenge T cell tolerance, until aPL production. Some AECA are thus induced by cell membrane structures, while others recognize "planted" antigens and possibly ligand-receptor complexes. A second group promotes procoagulant factor, and a third has the capacity to trigger apoptosis. Clearly, the most direct demonstration of the pathogenicity of AECA is the autoAb-induced murine model of vasculiltis.