Therapeutic angiogenesis to enhance collateral vessel growth is a promising strategy for the treatment of vascular occlusive diseases. Although local delivery of angiogenic growth factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) has shown favorable results, few studies have examined in detail the combined effects of VEGF and bFGF on collateral development. Here, we evaluated angiogenic activity and potential synergism of the naked plasmid DNA vectors encoding VEGF and bFGF by using the ex vivo angiogenesis assay and by comparing blood flow and limb loss score in a murine model of hindlimb ischemia (C57BL/6) where femoral artery was excised. In the ex vivo angiogenesis assay, VEGF+bFGF combination group displayed larger sprouting area than LacZ, VEGF, or bFGF group. Reflecting the capillary sprouting data, highest levels of VEGF and bFGF were secreted from the combination group. Consistent with these results, functional blood flow recovery at day 14 as measured by Laser Doppler Imaging was also highest in the VEGF+bFGF combination group followed by VEGF, bFGF, and LacZ control group. The limb loss score was also lowest (no necrosis) in the combination group, whereas there were 1~4 cases of limb or toe necrosis in other group. Currently, histological analyses of the ischemic muscle as well as expression of different genes are underway to examine the evidence of arteriogenesis and the possible involvement of early growth response factor-1 and cardiac ankyrin repeat protein. Our study has implications for the development of combined arteriogenic gene therapy that uses the two best characterized angiogenic growth factors, VEGF and bFGF.