The primary development of a male rather than a female gonad in mammals is determined by the presence of a Y chromosome. The other property unique to the Y chromosome is the occurrence of a cell-surface antigen (designated H-Y) which distinguishes male from female. Thus it was determined that male grafts were rejected by otherwise histocompatible females of the same inbred strain and later that H-Y-specific cytolytic T cells were produced by these grafted mice. When it was determined that females grafted with male skin produced antibody defining a serologically detectable male antigen (which may or may not be the same as H-Y), further immunogenetic analysis of this antigenic system became possible in terms of humoral and cellular factors. By using this assay it was demonstrated that the antigen was phylogenetically conserved and that it was expressed in the male mouse embryo as early as the 8-cell stage of development. The notion that H-Y was a single molecular species responsible for triggering the indifferent gonad to differentiate into the testis became a widely accepted hypothesis. In this report the H-Y antigenic system is traced historically from its original description to the role played in testis development. Data are presented which suggest that although H-Y is a male-specific factor and may play a role in male sex determination, it is unlikely that it is the primary inducer of testis differentiation.