For more than a decade, the notion that peripheral blood-derived stem cells engraft more rapidly than bone marrow-derived stem cells after high-dose therapy has dominated our thinking. Recently, reports that granulocyte colony-stimulating factor (G-CSF) induces a proteolytic marrow microenvironment have provided mechanistic support for that belief, compelling us to review our own experience of 29 consecutive transplants with HLA-identical blood and marrow stem cells. In contrast to several reported randomized controlled trials, we found marrow stem cells engraft just as rapidly (median day 11 for granulocytes over 500/microl and median day 17 for platelets over 20,000/microl) as blood stem cells (median day 12 and median day 19, respectively) if the donor is treated with G-CSF in the same manner before marrow harvest as the donor is treated with G-CSF before leukapheresis. These observations with healthy HLA-identical donors confirm the results of our prior randomized autotransplant study. We propose the concept that the level of activation of the stem cells (induced by G-CSF) determines engraftment kinetics and not the anatomical site of derivation.