Chemically distinct CXCR4 antagonists mobilize progenitor cells by different mechanisms. AMD3100 treatment generates a CXCL12 gradient across the sinusoidal endothelium, which supports migration of HPCs and MPCs from the bone marrow into the circulation. On the other hand, KRH3955 directly disrupts CXCR4-mediated retention of HPCs, resulting in their mobilization, but does not generate the CXCL12 chemokine gradient critical for MPC mobilization.