In the mixed allogeneic reconstitution (B10 + B10.D2----B10) model, alloresistance to engraftment of allogeneic donor results if the syngeneic component of the mixed bone marrow inoculum is not depleted of Lyt-2+ cells before transplantation. Resultant experimental animals repopulate as fully syngeneic, reject B10.D2 skin allografts, and are reactive to B10.D2 lymphoid cells in vitro, as assessed by mixed lymphocyte culture proliferative and cellular cytotoxicity assays. In contrast, depletion of Lyt-2-reactive cells from the syngeneic component of the mixed bone marrow inoculum results in mixed lymphopoietic chimerism and specific in vivo transplantation tolerance to B10.D2 allogeneic donor skin grafts and in vitro unreactivity to B10.D2 lymphoid elements. Full reactivity to third party is evident both in vitro and in vivo in these animals. This model may be helpful in further study of the syngeneic host-type cell phenotypes responsible for alloresistance to bone marrow engraftment.