This study quantified endogenous VEGF and VEGF receptor expression in limbs of patients with chronic critical limb ischaemia (CLI).Skin and muscle biopsies were obtained from the legs of 25 patients undergoing limb amputation for CLI. Samples were obtained at the amputation level (thigh or calf) and, distally, from the foot and in the vicinity of ischaemic ulcers and gangrene. Control biopsies were obtained from patients undergoing amputation for non-arterial reasons or knee arthroplasty (n=7). VEGF protein levels in tissue lysates were measured by ELISA, and VEGF and KDR mRNA levels were determined using quantitative PCR.At the amputation level, VEGF protein and VEGF and KDR mRNA levels in CLI limbs were similar to those in controls. In the foot VEGF mRNA in skin (P=0.005) and VEGF protein levels in muscle (P=0.02) were elevated compared to levels in a proximal biopsy from the same limb. VEGF and KDR mRNA levels in the vicinity of gangrene/ulcers (VEGF P=0.01, KDR P=0.03) also were elevated.VEGF expression is not deficient in CLI. Indeed, it is elevated at distal sites in the ischaemic limb. These findings question the rationale for VEGF supplementation in CLI.