The purpose of the proposed investigation is to better characterize the reactive lymphoid cells and serum blocking factors in operationally tolerant animals. This will be accomplished by the development of specific anti-rat T-cell reagents and by the identification of functionally distinct subpopulations of rat lymphoid cells using quantitative MLC and CML assays. Studies will be undertaken in H-2 recombinant mice to establish which antigens determine immunologic reactivity in tolerant hosts and to define which genetic mechanisms control responsiveness to these antigens. In vivo mechanisms of importance in transplantation tolerance will also be evaluated. These studies will critically test the hypothesis that subpopulations of lymphoid cells in tolerant animals may demonstrate different patterns of unresponsiveness to alloantigens.