The suboptimal return of hematopoietic precursors after bone marrow transplantation is suggestive of a limited bone marrow reserve in recipients of allografts. The problem does not appear to lie in the ability to produce some of the well-known hematopoietic growth factors such as G-CSF or activities considered to stimulate megakaryocytopoiesis. The persistence of factor production in patients with slow returning counts is suggestive of either a defect in the repopulating cells or in the function of the microenvironment that is not reflected in the production of factors that can be measured in the plasma. A defect in the graft may be overcome by altering the composition of engrafting cells. As seen in autologous transplants the addition of peripheral blood stem cells may be effective in reducing the period to engraftment. Putative defects in the microenvironment have to be addressed by further studies. Exogenously added stroma related factors such as kit ligand or IL-11 may be effective in correcting the deficiency.