The stated object of the grant proposal was to further elucidate sex differences. The focus of the work has been on early embryogenesis. The first difference that can be identified after fertilization is the production of H-Y antigen in the male and lyonization of the second X-chromosome in the female. An H-Y antigen has possibly been observed as early as eight cells in the male and has been found in all adult tissue studied. The second X-chromosome inactivates and appears to contribute few gene products to the growing cells in the female. The exception to this appears to be the germ cells. The germs cells may not inactivate the second X-chromosome or if they do inactivate it, the chromosome is reactivated before meiosis. There is indirect evidence that a Y-bearing primordial germ cell may produce the H-Y antigen and use the antigen to direct the early testicular development. To examine the interaction of germ cells and genital ridge cells, mosaic mice have been produced. Thus, an opportunity has been provided to evaluate the interaction of germ cells of one sex karyotype with genital ridge cells of a different sex karyotype. Mosaic mice (B6D2F1/J yields (reversibly) ICR) have been produced and I am studying the mice to determine which cell line is being transmitted to the offspring. Other investigators have shown that a murine sex mosaic will only produce offspring whose karyotype and phenotype are the same. I am studying the expression of H-Y antigen and female mice that produce only one line. The initial structure of the project is as follows: First, mice are produced; then, females are tested for H-Y antigen.