This is a proposal to study the genetics of histocompatibility antigens in man and mice. It will include studies on the segregation of HL-A antigens in human population and linkage between HL-A, lymphocyte activating determinants (LAD) and immune response (Ir) genes in selected families. Antisera previously prepared will be purified by a series of absorption and elution steps to provide reagents reacting only against LAD or only against HL-A. Initial definition of LAD will be by stimulation of lymphocytes from donors known to be homozygous at the major histocompatibility locus; this will be replaced by serological procedures as the LAD antigens become defined. We propose also to study factors that alter the surface of the leukemic cell and to determine if cell surface changes affect the homing of lymphocytes in malignant disease. We wish to investigate linkage disequilibrium between the HL-A and H-2 determinants and to determine whether HL-A or genes linked to HL-A exert selective effects. Some aspects of the studies relate to development, some to susceptibility to disease and others to the genetics of immunity to tumors and to transplanted tissues.