Depletion of donor CD6+ cells in HLA-identical allogeneic bone marrow transplantation has been reported to reduce graft-versus-host disease without interfering with engraftment. We have established an immunomagnetic cell separation technique capable of producing a 2-3 log depletion of CD6+ cells. Median recovery of CD6- cells and hematopoietic progenitor cells was 65-70%, and cell viability was unaffected. Significant numbers of CD2+, CD3+ cells responsive to phytohemagglutinin (PHA), OKT3, recombinant interleukin-2 (rIL-2), and allogeneic cells remained after depletion, and the number of cells able to respond to stimulation with PHA and IL-2 in vitro was reduced by only 1-2 log. These observations are not easily reconciled with the ability of CD6 depletion to prevent GVHD, but raise the question whether the depletion causes a sufficient reduction of the T cell load or removes a critical T cell subset.