It is hypothesized that the underlying immunoregulatory dysfunction in systemic lupus erythematosus (SLE) is altered recognition by T cells of self class II major histocompatibility antigens (Ia). The resultant cellular autoreactivity would directly cause certain of the immunopathological manifestations of SLE. The perception by T cells of self non-MHC antigens in the context of altered Ia on antigen presenting cells would also stimulate specific help for autoantibody production. Autoimmunity induced by the graft-versus-host reaction is an experimental model that illustrates this potential mechanism (A. G. Rolink, S. T. Pals, and E. Gleichmann, J. Exp. Med. 157, 755, 1983; R. A. Eisenberg, S. Y. Craven, and P. L. Cohen, Arth. Rheum. 26, S19, 1983).