In the present study, we tested the hypothesis that walking intolerance in intermittent claudication (IC) is related to both slowed whole body oxygen uptake (VO2) kinetics and altered activity of the active fraction of the pyruvate dehydrogenase complex (PDCa) in skeletal muscle. Ten patients with IC and peripheral arterial disease [ankle/brachial index (ABI)=0.73 +/- 0.13] and eight healthy controls (ABI=1.17 +/- 0.13) completed three maximal walking tests. From these tests, averaged estimates of walking time, peak VO2 and the time constant of VO2 (tau) during submaximal walking were obtained. A muscle sample was taken from the gastrocnemius medialis muscle at rest and analysed for PDCa and several other biochemical variables. Walking time and peak VO2 were approx. 50% lower in patients with IC than controls, and tau was 2-fold higher (P<0.05). tau was significantly correlated with walking time (r=-0.72) and peak VO2 (r=-0.66) in patients with IC, but not in controls. PDCa was not significantly lower in patients with IC than controls; however, PDCa tended to be correlated with tau (r=-0.56, P=0.09) in patients with IC, but not in controls (r=-0.14). A similar correlation was observed between resting ABI and tau (r=-0.63, P=0.05) in patients with IC. These data suggest that the impaired VO2 kinetics contributes to walking intolerance in IC and that, within a group of patients with IC, differences in VO2 kinetics might be partly linked to differences in muscle carbohydrate oxidation.