OBJECTIVE This study sought to elucidate the mechanisms responsible for the benefits of small muscle mass exercise training in patients with chronic heart failure (CHF). BACKGROUND How central cardiorespiratory and/or peripheral skeletal muscle factors are altered with small muscle mass training in CHF is unknown. METHODS We studied muscle structure, and oxygen (O(2)) transport and metabolism at maximal cycle (whole-body) and knee-extensor exercise (KE) (small muscle mass) in 6 healthy controls and 6 patients with CHF who then performed 8 weeks of KE training (both legs, separately) and repeated these assessments. RESULTS Pre-training cycling and KE peak leg O(2) uptake (Vo(2peak)) were ~17% and ~15% lower, respectively, in the patients compared with controls. Structurally, KE training increased quadriceps muscle capillarity and mitochondrial density by ~21% and ~25%, respectively. Functionally, despite not altering maximal cardiac output, KE training increased maximal O(2) delivery (~54%), arterial-venous O(2) difference (~10%), and muscle O(2) diffusive conductance (D(M)O(2)) (~39%) (assessed during KE), thereby increasing single-leg Vo(2peak) by ~53%, to a level exceeding that of the untrained controls. Post-training, during maximal cycling, O(2) delivery (~40%), arterial-venous O(2) difference (~15%), and D(M)O(2) (~52%) all increased, yielding an increase in Vo(2peak) of ~40%, matching the controls. CONCLUSIONS In the face of continued central limitations, clear improvements in muscle structure, peripheral convective and diffusive O(2) transport, and subsequently, O(2) utilization support the efficacy of local skeletal muscle training as a powerful approach to combat exercise intolerance in CHF.