Abstract Any physiological system that has as its output an activity that is biodestructive and ridding must have a way of distinguishing the host (self) from that which is other (nonself). The setting in which autoimmunity can be analyzed depends, in part and unavoidably, on the way in which the normal self (S)–nonself (NS) discrimination is accomplished. Any discussion of autoimmunity should include one’s view of this latter. To this end, a pathway for the normal S–NS discrimination will be proposed. Then, a mechanism for the determination of effector class will be considered as autoimmune disease is consequent to it. Experiments challenging both the proposed model of normal behavior, as well as that of the extrapolation to autoimmunity, will be cited along with a discussion of some of the elements which, if rendered defective, would result in autoimmunity. The goal is to see how far this particular abstraction based largely on the logic of evolutionary biology can meaningfully guide understanding of the disease.