Transfusion-related acute lung injury is seen following the transfusion of blood components. The reported incidence is approximately 1 in 2000 transfusions. Clinically, it is similar to adult respiratory distress syndrome. The pathophysiology is unclear but has been attributed to HLA antibodies, granulocyte antibodies, and more recently to biologically active mediators in stored blood components. We report a case with laboratory evidence that supports the role of biologically active mediators in the pathogenesis of transfusion-related acute lung injury. To our knowledge, the case reported here is the first to use lipid extractions of patient samples to determine that lipid-priming activity was present at the time transfusion-related acute lung injury was identified clinically.