EPCs were first described in 1997 when Asahara et al1 identified a population of mononuclear cells in the blood capable of differentiating into endothelial cells in vitro. It was proposed that these circulating progenitor cells may contribute to angiogenesis and vasculogenesis (formation of new blood vessels). Currently there are no specific markers to identify EPCs in mice or humans, but as EPCs proliferate clonally and produce colonies in vitro, specific colony assays can be generally performed to quantify numbers of EPCs in blood and tissues. In these assays, mononuclear cells are plated onto fibronectin or gelatin and grown in the presence of endothelial growth factors (including vascular endothelial growth factor [VEGF]). It is now clear that there are two distinct subsets of EPCs: the first derived from hematopoietic lineage (also known as early outgrowth EPCs [EOG-EPCs]) and the second from endothelial lineage (late outgrowth EPCs [LOG-EPCs]). EOG-EPCs are detected as colonies after 5 days of culture; they exhibit spindle-shaped morphology and have characteristics of both endothelial and monocytic cells. Thus, these cells express the leukocyte markers CD45, CD11c, and CD14, and the endothelial markers CD31 and VEGF receptor-22 (Fig 1). Importantly, EOG-EPCs are not believed to directly form new vessels, but they have been shown to secrete key proangiogenic factors, such as VEGF-A, CXCL12 (stromal derived factor-1), and insulin-like growth factor-1, and it is therefore suggested that they may promote angiogenesis/vasculogenesis through a paracrine mechanism.3 Interestingly, Asosingh et al4 recently reported that in a murine model of allergic airways disease, EOG-EPCs were isolated that on contact with activated endothelium produced the chemokine CCL11 (eotaxin). This suggests that the secretome of EOG-EPCs will change dependent on their inflammatory context and, as such, raises the possibility that the functional impact of specific progenitor cell populations will be disease dependent. In addition, aberrant progenitor cell activity may also contribute to disease. Indeed it has been reported that EOG-EPCs isolated from mice with hypoxia-induced pulmonary hypertension (PH) were defective in their ability to support angiogenesis,5 suggesting that the pathogenesis of this disease may be due in part to dysfunctional progenitor cells.