SummaryTransplantation of untreated F344 rat bone marrow into irradiated B10 mouse recipients (non-TCD F344 -> B10) to produce fully xenogeneic chimeras resulted in stable xenogeneic lymphoid chimerism, ranging from 82% to 97% rat . Survival of animals was excellent, without evidence for GVH disease. The specificity of tolerance which resulted was highly donor-specific ; MHC disparate third party mouse and rat skin grafts were promptly rejected while donor-specific F344 grafts were significantly prolonged (MST >130 days) . Multi-lineage rat stem cell-derived progeny including lymphoid cells (T and B-lymphocytes), myeloid cells, erythrocytes, platelets, and natural killer (NK) cells were present in the fully xenogeneic chimeras up to 7 months after bone marrow transplantation . Immature rat Tlymphocytes matured and acquired the a/# Tcell receptor in the thymus of chimeras in a pattern similar to normal rat controls, suggesting that immature Tlymphocytes of rat origin could interact with the murine xenogeneic thymic stroma to undergo normal maturation and differentiation . This model may be useful to study the mechanisms responsible for the induction and maintenance of donor-specific transplantation tolerance across a species barrier.