BACKGROUND: The aim of this study was to disentangle the contribution of muscular vs pulmonary oxidative stress during endurance exercise in patients with COPD. METHODS: Fifteen COPD patients and 10 healthy age-matched controls performed a continuously submaximal single leg ergometer test (40% of peak workload) for 20 min or until they stopped (Tlim). Venous blood, urine samples and exhaled breath condensate were sampled before, immediately and 2h after exercise. RESULTS: Tlim was lower in COPD than controls (p < 0.01). No exercise-induced systemic inflammation (IL-6, TNF-alpha) was found in the groups. Urinary malondialdehyde (MDA) and uric acid (p < 0.05) were increased in COPD whereas erythrocyte GSSG/GSH tended to be increased in COPD compared to controls after exercise (p = 0.08). Despite the relatively low cardioventilatory response to this localized muscle exercise, hydrogen peroxide (H(2)O(2)) in breath condensate significantly increased in COPD (p < 0.01). NF-kappaB DNA binding activity of p50 in peripheral blood monocytes was elevated after exercise in both COPD (p < 0.01) and controls (p < 0.05), whereas p65 protein was not altered. CONCLUSION: COPD patients showed increased pulmonary and systemic oxidative stress after localized leg muscle exercise compared to healthy controls without evidence of increased levels of systemic inflammation.