Transfusion-related acute lung injury (TRALI) is currently ranked as one of the most serious complications of blood transfusion. It is believed that the majority of TRALI reactions are associated with the presence of HLA and neutrophil antibodies in the transfused products that stimulate the production of reactive oxygen species (ROS) by pulmonary neutrophils, which damages pulmonary vessel endothelium. There have been several animal models of human TRALI including, for example, ex-vivo lung and in-vivo models demonstrating how antibodies and biological response modifiers can induce recipient lung damage. Newer animal models have utilized monoclonal anti-MHC Class I antibodies that cause significant increases in excess lung water, lung vascular permeability and mortality. These latter models have, however, generated controversial findings as different laboratories have discovered widely varied mechanisms of lung damage e.g., Fc-dependent neutrophil activation versus pulmonary damage induced by activated macrophages and complement. This session will have three speakers to highlight the various animal models of TRALI and discuss the controversies associated with them. It will attempt to formulate a unified hypothesis of how TRALI pathophysiology is mediated.