The analysis will be continued of the tolerogenic capacity of the alloantigens determined by the various sub-regions of the major histocompatibility complex in mice, especially with regard to various H-2 mutational differences at the K end of the complex. We have already found that in hamsters, 5 days after immunization with allogeneic cells, there is a reduction in the MLR responsiveness of splenic cells, as compared with the responsiveness of these cells 3 days after antigenic exposure. Experiments will be conducted to elucidate the basis of this suppression, paying particular attention to a suggestion that macrophages may play a significant role. Preliminary findings that immunization of mice of various strains with viable F9 teratocarcinoma cells, which share an antigenic determinant with sperm and embryos of many species, leads to antibody formation and impairment of conception will be followed up. Particular emphasis will be placed on the analysis of the mode of acion of this "abortifacient" and its nature. Using inverted allografts of tail skin in rats, a study will be made of the subcutaneous milieu as an immunologically privileged site. Fat pads will also be studied as host sites for allografts. Transepithelial migration of lymphoid cells will be studied further using F1 hybrid rats in which a blind loop ileostomy has been established. Parental strain lymphocytes will be introduced into the intestinal lumen, and graft-versus-host reactivity will be assessed by analysis of the villous epithelium, lamina propria, Peyer's patches, and draining lymph nodes. Coupled with determination of migratory patterns using radiolabeled cells in this system, these studies should answer the long-standing question concerning the ability of lymphoid cells to traverse intestinal epithelium, and could provide a useful assay for GVH potential of lymphoid cell populations, especially those in mammary secretions.