In man, the Major Histocompatibility Complex (MHC) is called “the human leukocyte A (HLA) system", whereas, for example, it is H-2 in mice, Antigen B (AgB) in rats, and B in chickens. The MHCs control strong transplantation antigens, play a fundamental role in the cooperation of cells in thymus-dependent immune responses, contain immune response (Zr) genes and some complement coding genes, and control susceptibility and resistance to a diversity of diseases. The HLA-D antigens are identified by the so-called mixed lymphocyte culture (MLC) reaction (MLR) in which lymphocytes from two different individuals are mixed and cultured in vitro. This reaction is based on the facts that lymphocytes carry both HLA-D antigens and receptors for foreign HLA-D antigens not possessed by the lymphocyte donor, and lymphocytes with such receptors under appropriate conditions will respond in vitro by proliferation, which can be measured by the uptake of certain substances. This chapter mainly summarizes the works dealing with the identification of human lymphocyte activating determinants (LADs) recognized by secondary MLR with special reference to the genetics of the PLT in man.