Systemic inflammation is induced during extracorporeal circulation, resulting in an increased bleeding tendency and endothelial cell activation. Lungs from seven piglets were perfused by autologous blood in an extracorporeal circuit, where the lungs and the left atrium were attached to polyvinyl chloride (PVC) tubings and the blood circulated by a roller pump. The trachea was intubated and attached to a ventilator. The lungs maintained good gas exchange, despite a slight increase in lactate levels. Plasma tPA increased slightly over time, suggesting endothelial cell activation. Activation of inflammatory systems was reflected in increased levels of plasma interleukin (IL)-6 and IL-10. A model for the study of lung endothelial activation during extracorporeal circulation has been shown to be reproducible. The lung tissue was shown to be capable of gas exchange and activation of endothelial cells and procedure-induced inflammation were noted.