Rationale: Severe pulmonary arterial hypertension (PAH) is characterized by the formation of plexiform lesions and concentric intimal fibrosis in small pulmonary arteries. The origin of cells contributing to these vascular lesions is uncertain. Endogenous endothelial progenitor cells (EPCs) are potential contributors to this process. Objectives: To determine whether progenitors are involved in the pathobiology of PAH. Methods: We performed immunohistochemistry to determine expression of progenitor cell markers (CD133 and cKit) and the major homing signal pathway stromal-cell derived factor-1 (SDF-1) and its chemokine receptor (CXCR4) in lung tissue from patients with idiopathic PAH, familial PAH, and PAH associated with congenital heart disease. 2 separate flow cytometric methods were employed to determine peripheral blood circulating numbers of angiogenic progenitors. Late outgrowth progenitor cells were expanded ex vivo from peripheral blood in patients with mutations in BMPRII and functional assays of migration, proliferation and angiogenesis undertaken. Measurements and Main Results: There was a striking upregulation of progenitor cell markers in remodeled arteries from all patients with PAH specifically in plexiform lesions. These lesions also displayed increased SDF-1 expression. Circulating angiogenic progenitor numbers in PAH patients were increased compared with controls and functional studies in late outgrowth progenitor cells from PAH patients with BMPRII mutations revealed a hyperproliferative phenotype with impaired ability to form vascular networks. Conclusions: These findings provide evidence for the involvement of progenitor cells in the vascular remodeling associated with PAH. Dysfunction of circulating progenitors in PAH may contribute to this process.