Antibodies recognizing non-bilayer phospholipid arrangements (NPA) in membrane models and in cell membranes in vivo, triggered an autoimmune-like disease in mice. This exhibited features similar to human lupus and was induced by injecting mice either with the H308 monoclonal antibody specific to NPA, with sera from mice which already had developed the autoimmune disease, or with liposomes treated with the NPA inductors chlorpromazine or procainamide; or with these NPA inductors alone. All these procedures revealed the involvement of antibodies to non-bilayer phospholipids in inducing this autoimmune-like disease. Unraveling the mechanisms of these antibodies might contribute to a better understanding of the molecular and immunological basis of autoimmune diseases like lupus and, hopefully, towards the development of better therapeutic strategies.