OBJECTIVES: To review clinical and experimental evidence that exercise to the onset of calf pain in patients with intermittent claudication results in an inflammatory response, and to consider whether repeated inflammatory events induced by therapeutic exercise training may lead to progression of atherosclerosis. METHODS: A literature search was performed to identify studies measuring biochemical markers of exercise-induced ischaemia-reperfusion injury in patients with intermittent claudication. Current theories of atherogenesis were reviewed and the use of acute-phase proteins as potential markers of vascular disease explored. RESULTS: Exercise to the onset of calf pain results in an inflammatory response with free radical formation, neutrophil activation and systemic vascular endothelial damage. Acute-phase proteins such as C-reactive protein and serum amyloid A protein have exciting potential use as stable biochemical markers of disease in claudication. CONCLUSIONS: Further studies are needed to determine the effect of long-term exercise training on exercise-induced inflammation in claudication. Early work suggests, in fact, that exercise attenuates this inflammatory response. If this were confirmed then it would support the clinical impression that exercise training is beneficial in terms of symptomatic improvement and cardiovascular health in patients with intermittent claudication.