Pulmonary insufficiency is occasionally a life-threatening sequel to severe nonthoracic trauma. A similar disturbance of pulmonary function may be a feature of hepatic cirrhosis, fulminant hepatic failure, liver homotransplantation and major hepatic resection for blunt injury. In addition to the respiratory changes, other associations common to both post-traumatic pulmonary insufficiency and liver disease are disturbance of consciousness and susceptibility to infection by organisms normally found in the gastrointestinal tract. If failure of some aspect of liver function is responsible for the development of pulmonary insufficiency, it is likely that it is the hepatic reticulo-endothelial cells rather than the parenchymal cells which are concerned, because hepatic parenchymal cell failure is not a feature of post-traumatic pulmonary insufficiency. It is suggested that the hepatic reticuloendothelial system normally protects the lungs by acting as a prepulmonary filter removing and inactivating noxious macromolecular and particulate matter in the blood, such matter arising mainly from the intestine and the blood coagulation and fibrinolytic systems. Experimental evidence indicates that hypovolemia increases the load of circulating phagocytosable material and depresses activity of the hepatic reticuloendothelial system, while trapping of the pulmonary reticuloendothelial system is considerably enhanced. This noxious material, normally dealt with by the hepatic reticuloendothelial system, may accumulate during and after hypovolemia in active form in the lungs as a result of the action of three mechanisms: direct pulmonary reticuloendothelial phagocytosis from the blood, transfer in hepatic reticuloendothelial cells from liver to lungs and uptake from the blood by polymorphonuclear leukocytes which become sequestered in the lungs. The ensuing pulmonary injury caused by this material may then be manifested by progressive pulmonary insufficiency and the impairment of activity of the hepatic reticuloendothelial system by the presence of gram-negative infection. The reticuloendothelial system has been largely neglected in man, and it is considered that evaluation of reticuloendothelial activity in injured patients may lead to the definition of a syndrome of failure of the reticuloendothelial system of which pulmonary insufficiency may be an integral part.