The purpose of this project is to identify distinct steps in the functional differentiation and maturation of cells of the immune system of mice and to understand the controls of such differentiation. Five areas of investigation are contemplated: (1) Mechanisms of alloantigen recognition and graft rejection for allogeneic bone marrow cells as compared with recognition and rejection of grafts of different histological type, (2) Genetic and immunologic determination of histoincompatibility specific for hemopoietic cells (antigens underlying allogeneic and hybrid resistance), (3) Role and nature of immune response genes in the regulation of allograft reactivity to hemopoietic cells, (4) Mechanisms of antigen recognition and humoral antibody formation for immune responses to sheep erythrocytes, with particular emphasis on cooperation between bone marrow and thymus cells, and between macrophage-like cells and thymus or bone marrow cells, and (5) Relationship between effector cells of the humoral and the different cell-mediated immune responses. BIBLIOGRAPHIC REFERENCES: E. Bonmassar, C. Testorelli, P. Franco, A. Goldin, and G. Cudkowicz. Changes of the Immunogenic Properties of a Radiation-induced Mouse Lymphoma following treatment with Antitumor Drugs, Cancer Res., 35: 1957-1962 (1975). G. M. Shearer and G. Cudkowicz. Induction of Fl Hybrid Antiparent Cytotoxic Effector Cells: An in Vitro Model for Hemopoietic Histoincompatibility. Science 190:890-893(1975).