We have demonstrated that an individual mouse or rat can respond to antigen by producing both antibody directed against the antigen and antibody directed against the receptor for that antigen. In the mouse we have a plaque-forming cell assay for cells releasing each kind of antibody and we can manipulate the model to demonstrate that the reciprocal antibody responses can be autoregulatory. In the rat, the inference is extremely strong that antibody directed against the receptors for alloantigen can markedly suppress specifically cell mediated immunity in GVH disease, graft rejection and CMI in vitro. The chief objectives are to define the conditions which are optimal for generating anti receptor antibody and assess the effects of interaction of antibody with antireceptor antibody; i.e. assess the blocking effect of one on the other. For these studies we will need precise methods for measuring anti-receptor antibody directed against alloantigens using a plaque-forming cell assay and a radio immune assay. The development of such methods will be a major objective. BIBLIOGRAPHIC REFERENCES: Strayer, D.S., Lee, W.M.F., Rowley, D.A. and Kohler, H. Anti-receptor antibody. II. Induction of Long-Term unresponsiveness in neonatal mice. J. Immunol. 144, 728, 1975. Rowley, D.A., Fitch, F.W., Cosenza, H. and Leserman, L. The 3rd cell type required for the antibody response in vitro. In 'Mononuclear Phagocytes in Immunity, Infection and Pathology', ed. R. van Furth, Blackwell Scientific Publication Ltd., Oxford, Edinburgh, London and Melbourne, 1975.