Thirty-four patients with severe aplastic anemia were treated with cyclophosphamide or total body irradiation and an infusion of marrow from a genotypically HLA-identical sibling donor. Engraftment occurred in all patients but rejection was noted in 12. Mixed leukocyte culture (MLC) tests undertaken before grafting to determine donor-recipient histocompatibility were analyzed retrospectively. The response of patient cells to sibling cells in mixed culture was compared to the response of patient cells to cells of an unrelated individual and expressed as a relative response index (RRI). Of the 12 patients who showed positive RRI to donor leukocytes in pregraft MLCs, 9 rejected their grafts, wheras of 23 patients with negative RRI only three rejected their grafts (P LESS THAN 0.005). The results suggest that the MLC test can detect individuals who are most likely to reject their HLA identical sibling graft.