During normal bicycle exercise maximal fat oxidation is highest at moderate exercise intensities, whereas carbohydrate oxidation increases as exercise intensity increases. Although the exact regulation and control of substrate oxidation is still not fully understood, it has been suggested that fat oxidation at higher exercise intensities may be attenuated due to decreased pH and/or limited oxygen supply. We studied substrate utilization during graded one-leg exercise where muscle oxygen delivery is not limited and in contrast to whole body exercise an attenuation of fat oxidation during high intensity exercise was not observed. During exercise fat is recruited from exogenous and endogenous stores and the exogenous fatty acids may originate from albumin bound and/or very low density lipoprotein (VLDL) fatty acids. During graded one leg exercise VLDL- fatty acid uptake was non-significant and thus not affected by exercise intensity, whereas the plasma fatty acid contribution increased with exercise intensity. Thus implying that fat oxidation during exercise with a limited muscle mass is not attenuated during high intensity exercise¬. During whole body exercise including both arm and leg cycling the substrate utilization assessed by the respiratory quotient was similar across the limbs. Interestingly the plasma FA uptake expressed per kg limb lean body mass was markedly higher in the legs than the arms, whereas the limb glucose uptake was not different between limbs. A markedly higher lactate release was observed from the arms than the legs and overall this indicates that the contribution of exogenous versus endogenous substrate to limb substrate metabolism may differ between arm and leg muscle during whole body exercise. Financial support from the Danish National Research Foundation and the Danish Ministry of Culture Committee on Sports Research is gratefully acknowledged.