The 1B-peptide marker in the V-region of mouse immunoglobulin light chains is closely linked genetically to the Ly-3.1 thymocyte surface antigen. Inbred strains with these markers have a high incidence of spontaneous leukemia. The relationship among these phenomena will be studied by: 1) determining by genetic backcross the degree of linkage between 1B and Ly-3.1; 2) obtaining immunoglobulins enriched in 1B by ion-exchange methods; 3) developing an immunochemical assay for 1B; 4) investigating by protein structural methods the variability in purified 1B-positive light chains; 5) investigating by inhibition of cytotoxicity the possibility of structural similarity between 1B-positive immunoglobulin and Ly-3.1; 6) determining the incidence of spontaneous leukemia in the 1B-positive B6/Ly-2. 1, Ly-3.1 strain; 7) determining by immunoabsorption and cytotoxicity whether 1B-positive immunoglobulin binds to antigens of murine leukemia virions or leukemic cells. The foetal mouse thymus in organ culture will be used to study the role of the thymic epithelium in T-cell differentiation and leukemogenesis. Studies will include: 1) determining the pattern of radioactively labeled proteins (C14, S35, I131) of epithelial and lumphoid cells after varying periods of culture by autoradiography of two-dimensional polyacrylamide gels; 2) following proliferation and cell surface maturation of lymphoid cells present in the explanted tissue, and correlating these processes with gel electrophoretic patterns; 3) introducing lymphoide cells from various organs, syngeneic and allogeneic, into the cultured thymus at various times, and following their proliferation and antigenic maturation by cytotoxicity methods as above; 4) injecting RadLV directly into the cultured thymus, and following lymphoid cell mitosis, viral replication, and alterations in antigenic properties of cells and in their protein fingerprints; 5) studying thymic epitheliomas which restore immunocompetence to neonatally thymectomized mice by similar methods, since these may provide a source of specific thymic epithelial proteins in large quantities.