We have previously shown that in patients with peripheral ischemia serum concentration of vascular endothelial growth factor (VEGF) differs depending on the disease severity being the highest in subjects with critical leg ischemia (CLI), although no apparent neoangiogenic effect like collateral circulation was observed in their ischemic tissues. Therefore, the aim of present study was to assess the effective proangiogenic activity of sera from patients with peripheral ischemia. It was demonstrated that endothelial cells (HUVEC) incubated in medium enriched with 5% of sera from critical leg ischemia patients demonstrated greater proliferative activity than cells incubated with serum from healthy controls (p < 0.001). Also, their ability to form new sprouts in vitro was significantly greater when cultured in medium enriched with serum from patients with CLI (1025.85 &#177; 316.56) in comparison to serum of moderate leg ischemia (MOD) (371.96 &#177; 47.07) (p < 0.001) or controls. Thus, in patients with severe ischemia, VEGF is not only present in serum in considerably higher concentration than in healthy controls, but also is biologically active, able to evoke appropriate responses in tissues.