The basic embryonic plan of mammals is inherently feminine. Male development is due to two-step interventions of this basic plan: the Y chromosome directs the embryonic indifferent gonad to organize a testis instead of an ovary; the Y-organized testis synthesizes and secretes testosterone, which induces all the extragonadal masculine development. The Y chromosome plays no direct and appreciable role in extragonadal masculine development. Testicular organization, normally under the direction of the Y, is the function of the evolutionary conserved plasma membrane protein serologically detectable as H-Y antigen. Under specific circumstances, H-Y antigen may be expressed in the absence of the Y chromosome, thus producing XO and XX males. If H-Y antigen is not expressed, XY individuals develop as females. H-Y antigen is the first plasma membrane or cell surface protein to which a specific organogenesis function has been assigned.