After allogeneic bone marrow transplantation (BMT), patient hematopoietic and lymphoid cells are replaced by cells derived from the donor marrow. To document and characterize successful engraftment, host and donor cells must be distinguished from each other. We have used DNA sequence polymorphism analysis in 6 patients, at times varying, to determine reliably the host or donor origin of posttransplant cell populations and to compare these results with those obtained using red blood cell antigens and cytogenetics. Initially full engraftment was documented in all patients. In 1 patient a mixed lymphohematopoietic chimerism was documented 6 months after BMT and it reverted to donor hematopoiesis at 1 year post BMT. Posttransplant leukemic relapse was studied in two patients and shown to be of host origin in both cases. The DNA restriction fragment length polymorphisms (RFLP), are a powerful tool for the documentation of engraftment after BMT, to document mixed lymphohematopoietic chimerism and for the evaluation of leukemic relapse.