Using red cell phenotyping, cytogenetic analysis of blood lymphocytes, chromosome studies of bone marrow cells, and restriction fragment length polymorphism (RFLP) studies of peripheral blood cells, we demonstrated a high number of mixed chimeras after allogeneic bone marrow transplantation (BMT). Donor marrow from HLA-A, -B, and -DR identical, mixed lymphocyte culture (MLC) nonreactive siblings was depleted of 98% of lymphocytes using counterflow centrifugation. Thirty- two of 48 recipients (67%) appeared to be mixed chimeras at 6 months after transplantation. The high number of mixed chimeras is probably a result of lymphocyte depletion of the marrow graft and the high sensitivity of red cell phenotyping for the demonstration of minor cell populations (at levels as low as 0.01%). The probability of relapse- free survival from 6 months to 4 years after BMT was 85% for the mixed chimeras and 65% for the complete donor chimeras. We conclude that in this study, mixed chimerism is not associated with a higher incidence of relapse.