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The LFA-1 molecule is a member of the leukocyte adhesion complex (CD11/CD18) that is critical to adhesion and effector function of T cells and NK cells. Both T cells and NK cells play important roles in bone marrow graft rejection, and anti-LFA-1 MAbs inhibit in vitro T cell and NK cell cytotoxicity. We here describe the in vivo use of a monoclonal antibody to the alpha chain of LFA-1 (CD11a) to prevent rejection of T cell-depleted allogeneic bone marrow. Animals receiving anti-LFA-1 and 1100 cGy total-body irradiation showed improved hemopoietic and immunologic reconstitution one month after BMT when compared with animals receiving TBI alone. Animals in the anti-LFA-1 group showed significantly improved long-term survival, and had no deficits in long-term lymphohemopoietic reconstitution.