Endothelial progenitor cells (EPCs) may contribute to vascular repair. We have investigated the influence of the angiogenic chemokines growth-regulated oncogene (GRO-a) and stromal cell-derived factor (SDF-1a) on homing of human EPCs. EPCs were isolated from peripheral blood mononuclear cells and cultured for 7 days. Flow cytometry analysis revealed expression of VEGFR2, CD31, VE-cadherin as well as CXCR2 (GRO-areceptor) and CXCR4 (SDF-1a receptor). In contrast, mature endothelial cells did not express CXCR2. Similar quantitative differences were obtained by analyzing mRNA for CXCR2/CXCR4. Functionally, SDF-1a increased the EPC transmigration by 158±4% (P<0.001), while GRO-a showed no effect. Conversely, the EPC adhesion under laminar flow on fibronectin was increased after immobilization of GRO-a by 120±4% (P<0.05), while SDF-1a had no effect. In addition, the EPC adhesion on platelet-coated endothelmatrix was significantly reduced after blocking CXCR2, but not CXCR4. This was also confirmed by ex vivo perfusion of carotid arteries from ApoE-/-mice after wire injury. In addition, we identified a novel sub-population of circulating human CD34+/VEGFR2+/CXCR2+ cells. Hence, the axis GRO-a/CXCR2 plays a crucial role for the EPC adhesion, while SDF-1a affects mainly the EPC migration.