OBJECTIVE: To examine whether endogenous bradykinin mediates the endothelium-dependent vasomotor dysfunction induced by ischaemia-reperfusion injury, or the protection afforded by remote ischaemic preconditioning in vivo in man. DESIGN: Randomised double-blind, cross-over study. SETTINGS: Royal Infirmary of Edinburgh, Wellcome Trust Clinical Research Facility. PATIENTS: Twenty healthy male volunteers. INTERVENTIONS: Subjects were randomised to intravenous infusion of the bradykinin B(2) receptor antagonist, HOE-140 (100 μg/kg), or saline placebo in a double-blind, crossover trial. Ischaemia-reperfusion injury was induced in the non-dominant arm by inflating a cuff to 200 mm Hg for 20 min in all subjects. Ischaemia-reperfusion injury was preceded by three cycles of remote ischaemic preconditioning in the dominant arm in 10 subjects. MAIN OUTCOME MEASURES: Bilateral forearm blood flow was assessed using venous occlusion plethysmography during intra-arterial infusion of acetylcholine (5-20 μg/min). RESULTS: Acetylcholine caused vasodilatation in all studies (p