We have shown previously that donor-derived splenocytes can replace recipients' bone marrow and induce donor-specific tolerance (DST). We have also shown the usefulness of the chimeric state for the induction of DST. Further analysis of mixed splenocytes chimera, especially the role of each T cells in mixed splenocytes chimera, is indispensable issue for its clinical use. A chimeric state has been shown to achieve long-term survival in major histocompatibility complex (MHC)-mismatched grafts. The donor-derived splenocytes can replace recipients' bone marrow and induce DST. The long-term survival of allogeneic skin grafts was achieved without immunosuppressants. In this study we show the role of each T cell type in a splenocyte mixed chimera. This review provides a short summary of our original work, adding some supplemental interpretations. Mixed chimerism is thus considered an attractive approach for the induction of DST without the use of immunosuppressants. In this paper, we summarize some of the findings on mixed splenocyte chimeras and review mixed chimerism in recent organ transplantation.