Objective: The angiotensin converting enzyme (ACE) is a protease involved in the regulation of blood pressure as it generates the vasoconstrictor peptide angiotensin II as well as degrading the vasodilator peptide bradykinin. Recent studies have suggested that ACE may also be a marker of human hematopoietic stem cells but the functional role of the enzyme remains unclear. The purpose of this study was to assess the consequences of ACE deletion as well as ACE inhibition of the mobilization of hematopoietic progenitor cells (HPCs) in response to the pro- inflammatory cytokine granulocyte-colony stimulating factor (G-CSF). Methods and results: Immunohistochemistry of murine femurs demonstrated the presence of ACE in the cells lining the bone as well as in a small number of bone marrow cells. Progenitor cell mobilization from the bone marrow (G-CSF, 5 days) from wild- type and ACE-/- mice into the blood was then quantified by assaying the colony-forming-units (CFU-C) after 14 days in culture and more primitive progenitor cells were assessed by day- 12 colony forming units, spleen (CFU-S12) assay. Compared with wild-type mice, blood from ACE-/- mice displayed a 3-fold increase in the number of CFU-Cs formed. Moreover sublethally irradiated mice receiving mobilized blood cells from ACE-/- mice formed significantly more spleen colonies. Similarly, in wild-type animals, treatment with the ACE inhibitor Ramipril (10mg/kg/day, 5 days) before G-CSF administration also resulted in a significant increase in G-CSF induced hematopoietic progenitor cell mobilization. Conclusion: Taken together these findings indicate a new role for ACE in the bone marrow niche and in progenitor cell mobilization and suggest that some of the benefits of ACE inhibitor therapy may be linked to increased stem cell mobilization.