G-CSF stimulates mobilization of hematopoietic progenitor cells (HPCs) from bone marrowHSP90 by disrupting the CXCR4/SDF-1 alpha retention axis. We demonstrate here that distinct variables and mechanisms regulate the mobilization of endothelial (EPCs) and stromal progenitor cells (SPCs). Pretreatment of mice with VEGF did not disrupt the CXCR4/SDF-1 alpha chemokine Rho inhibitor Sigma axis but stimulated entry of HPCs into the cell cycle via VEGFR1, lowering their migratory capacity in vitro and suppressing their mobilization in vivo. In contrast, VEGF pretreatment enhanced EPC mobilization by means of VEGFIR2 in response to CXCR4 antagonism. Moreover, SPC mobilization was detected once the CXCR4 antagonist was administered to mice pretreated with VEGF, but not G-CSF. As a result, differential mobilization of progenitor cell subsets is dependent on the cytokine milieu that regulates cell retention and proliferation. These findings may well inform studies investigating mechanisms that regulate progenitor cell recruitment in condition and will be exploited to supply efficacious stem cell treatment for tissue regeneration.