Cellular components of the vascular system are developmentally diverse and display considerable phenotypic plasticity. Circulating myeloid cells can differentiate into endothelial progenitor cells (EPCs), or smooth muscle progenitor cells (SPCs) depending on the presence of specific extracellular cues: platelet-derived growth factor-BB (PDGF-BB) treatment of EPCs triggers differentiation into SPCs [1]. Such cells are potentially involved in repair of the vascular system, but could participate in disease processes, such as atherosclerosis [2]. Despite possible involvement of circulating stem cells in vascular health and disease, there are no published data characterising calcium signalling mechanisms that they utilise. Given the role of Ca²⁺ as a key cytoplasmic second messenger, this represents a deficit in understanding vascular stem cell biology. To address this issue, our laboratories characterised calcium signalling mechanisms present in EPCs, SPCs and differentiated human aortic smooth muscle cells (hASM). EPCs, SPCs and hASM express multiple subtypes of ryanodine receptor calcium release channel (RyRs) and L-type voltage-gated calcium channels (VGCCs). Levels of these proteins differ between cell types. Unstimulated cytoplasmic Ca²⁺ concentrations ([Ca²⁺]_c) were significantly lower in EPCs compared with the other cell types. This implies that differentiation of vascular progenitor cells toward a smooth muscle phenotype is associated with long-term increases in [Ca²⁺]_c and with alterations in calcium signalling machinery present. Vascular progenitors were stimulated with chlorocresol (CmC) to open RyRs, or by depolarisation with KCl to activate VGCCs. Both CmC and depolarisation caused rapid elevations in [Ca²⁺]_c in EPCs, SPCs and hASM, but magnitudes of these increases differ between the three cell types. Depolarisation-induced increases in [Ca²⁺]_c in EPCs indicate that these stem cells are functionally distinct from mature vascular endothelial cells, which do not express VGCCs [3]. Treatment of EPCs with PDGF-BB also triggers complex changes [Ca²⁺]_c within seconds of addition. These changes in [Ca²⁺]_c varied between individual cells and included decreases as well as increases in cytoplasmic levels of this ion. Overall, these studies indicate association between calcium signalling and differentiation toward a smooth muscle phenotype in vascular progenitor cells. Mechanisms by which calcium signals could modify vascular stem cell phenotype are currently under investigation within our laboratories.