BACKGROUND Successful extremity transplantations and replantations have to be performed within 6 h of amputation to avoid irreversible tissue loss. This study investigates ex vivo the technical feasibility and the limb preservation potential of extracorporeal whole blood perfusion in a porcine model. METHODS Forelimbs of eight large white pigs were divided into paired groups: I perfusion group, II contralateral cold ischemia controls. In group I axillary arteries and veins were cannulated and perfusion with anticoagulated autologous blood was performed for 12 h; O(2), CO(2), Hb, lactate, potassium, pH, and muscle contractility were monitored. Tissue biopsies were examined by histology and immunofluorescence. Group II was stored at 4°C. RESULTS Continuous limb perfusion could be performed in all extremities of group I for 12 h. pH was maintained normal and potassium controlled with insulin and glucose. Lactate levels increased initially during perfusion due to the lack of a metabolizing liver. Muscle stimulation was possible throughout the entire perfusion, whereas a complete loss of response was noted in cold ischemia controls. Minor tissue damage was observed histologically and by immunofluorescence in group I, whereas the samples of group II were apparently preserved with the exception of a loss of endothelial heparan sulfate. CONCLUSIONS The tissue preserving potential and the feasibility of extremity perfusion using common extracorporeal blood circulation techniques was demonstrated in this ex vivo study. The results encourage further investigations in prolonged perfusion followed by limb replantation. This approach harbors promising clinical potential for extremity preservation in extremity transplantation and replantation.