We compared the effects of intraosseous BMT with those of standard i.v. BMT on the efficacy on donor-cell engraftment into the BM and lymphoid organs across an MHC barrier in rats. Twenty-four intraosseous and 24 i.v. BMTs were performed from 48 ACI (RT1 a ) donors to 48 Lewis (RT1 l ) recipients. Each transplant group received either intraosseous or i.v. BMT. Groups I and II served as controls without immunosuppression (n ¼ 16); groups III and IV received cyclosporine monotherapy (n ¼ 16); and V and VI received ab-TCR monoclonal antibody and cyclosporine A (ab-TCR/CsA) for 7 days (n ¼ 16). In each group, four rats received 35 Â 10 6 transplanted bone marrow cells (BMCs) and four received 70 Â 10 6 cells. All animals survived without GVHD. Mean (7s.d.) donorcell engraftment into BM of recipients after intraosseous BMT was 7.9% (71.3%) in recipients receiving ab-TCR-CsA and 70 Â 10 6 BMCs, and 4.2% (71.4%) in recipients after i.v. transplantation. The seeding efficacy of donor cells into lymphoid tissue was greater after intraosseous BMT and ab-TCR-CsA than after standard i.v. transplantation. In our model, intraosseous BMT facilitated donor-cell engraftment under short-term immunodepletive ab-TCR/CsA protocol, which resulted in a temporary state of immune unresponsiveness.