Autoimmunity has been considered to represent termination of the natural unresponsive state to self {Weigle 1977). It was originally thought that selftolerance is achieved by elimination of self-reactive lymphocyte clones early in ontogeny (Burnet 1959). However, we now know that such self-reactive clones are normally present in the intact immune system {Clagett & Weigle 1974, Cohen & Wekerle 1973, Bankhurst et al. 1973, Bankhurst & Williams 1975, Sawada et al. 1977, Wigzell 1977) and that self-recognition, based on the complementarity of interacting structures on T cells, B cells and macrophages, is the basis for immune responses {Katz 1977). The prevailing current concept is that self-recognition processes, essential to immune and possibly other physiologic systems, are normally controlled or suppressed by one or more mechanisms that counteract deleterious autoreactive consequences. A variety of events, either exogenous or endogenous, could tip the balance of such regulatory supervision, thereby upsetting its normal damping effect so that harmful autoreactivity is the outcome. Sometimes this imbalance is only transient, superceded by reestablishment of the normal damping mechanism and a return to control over the system. At other times, the defect is permanent, leading to a progressive increase in harmful autoreactivity. This sequence seems to account for the chronic autoimmune phenomena seen in some strains of mice and in certain human diseases, most notably systemic lupus erythematosus (SLE), the prototypic autoimmune disease.