BACKGROUND The purpose of this study was to determine the effects of systemic exercise training on endothelium-mediated arteriolar vasodilation of the lower limb and its relation to exercise capacity in chronic heart failure (CHF). Endothelial dysfunction is a key feature of CHF, contributing to increased peripheral vasoconstriction and impaired exercise capacity. Local handgrip exercise has previously been shown to enhance endothelium-dependent vasodilation in conduit and resistance vessels in CHF. RESULTS Twenty patients were prospectively randomized to a training group (n=10, left ventricular ejection fraction [LVEF] 24+/-4%) or a control group (n=10, LVEF 23+/-3%). At baseline and after 6 months, peak flow velocity was measured in the left femoral artery using a Doppler wire; vessel diameter was determined by quantitative angiography. Peripheral blood flow was calculated from average peak velocity (APV) and arterial cross-sectional area. After exercise training, nitroglycerin-induced endothelium-independent vasodilation remained unaltered (271% versus 281%, P=NS). Peripheral blood flow improved significantly in response to 90 microg/min acetylcholine by 203% (from 152+/-79 to 461+/-104 mL/min, P<0.05 versus control group) and the inhibiting effect of L-NMMA increased by 174% (from -46+/-25 to -126+/-19 mL/min, P<0.05 versus control group). Peak oxygen uptake increased by 26% (P<0.01 versus control group). The increase in peak oxygen uptake was correlated with the endothelium-dependent change in peripheral blood flow (r=0.64, P<0. 005). CONCLUSIONS Regular physical exercise improves both basal endothelial nitric oxide (NO) formation and agonist-mediated endothelium-dependent vasodilation of the skeletal muscle vasculature in patients with CHF. The correction of endothelium dysfunction is associated with a significant increase in exercise capacity.