Most current theories to explain autoimmunity either implicate dysregulation within the immune system as the cause, and regard the diseased tissue as the victim,1,2or speculate on idiotype anti-idiotype cross-reactions.3,4There are objections to both views. The hypothesis presented here argues that autoimmunity is not itself an entity, but a physiological response to sustained excess antigen turnover in diseased tissues (the primary lesion) and fundamentally no different from the response to foreign antigen. Those who develop clinical disease are viewed as high responders to critical antigens. High responder status is determined by immune response (HL-linked) genotype, not immune dysregulation.