In seven patients with chronic heart failure (CHF) and six controls, we examined (a) resting and post-exercise muscle vascular endothelial growth factor (VEGF) mRNA levels and (b) their relationship with muscle structure and function. Muscle biopsies were taken after 30 min of single-leg knee-extensor exercise at 50% of maximum work rate (50% WR(max)) from both the exercised and rested legs. Muscle blood flow (.Q) and O(2) uptake .VO(2) were measured during exercise. Resting VEGF mRNA levels were not different between patients and controls and both groups upregulated VEGF mRNA equally in response to acute exercise. Patients had lower .Q, .VO(2), and mitochondrial density but similar capillarity and fiber area. These findings reveal a normal basal level of muscle VEGF mRNA, its appropriate upregulation in response to acute exercise and, despite increased vascular resistance during exercise, a normal skeletal muscle vascular structure in patients with CHF.