Autoimmunity and autoimmune disease are not the same. Autoimmunity is a normal consequence of aging, potentially reversible and possibly physiological. Autoimmune disease is dependent on genetic, viral, hormonal and psychoneuroimmunological factors. Aside from the apparently normal regulation of autoimmune responses by immune response genes, little is known about other genetic factors. Here, Norman Talal and John Mountz propose the term autogene to describe non-MHC genes which directly or indirectly interfere with important immunoregulatory actions. When mutated or otherwise genetically altered (e.g. by retrotransposon insertion), these genes predispose to immune dysregulation, lymphoproliferation and autoimmunity.