To identify mechanisms potentially contributing to graft failure, 19 leukemic recipients of T-cell-depleted marrow transplants who failed to engraft following a transplant of HLA identical sibling marrow depleted of T cells by soybean agglutinin (SBA) and sheep erythrocytes (E) were evaluated. Peripheral blood mononuclear cells isolated at the time of failure were consistently of host origin, bearing the phenotype of suppressor T cells (CD3+, CD8+, Leu 7+). A direct cytolytic effect on 51Cr-labeled donor-derived target cells was not detected, a finding that contrasts with the donor-specific cytotoxic host T lymphocytes that have been regularly observed in patients rejecting HLA nonidentical SBA -E- BMTs. However, these host T cells did exhibit a strong and specific suppressive activity against the donor marrow CFU- GM in vitro. Furthermore, in contrast to prior findings in durably engrafted recipients of SBA -E- BMTs, the lymphocytes isolated prior to or at the time of graft failure lacked natural killer surface antigen expression and effector function.