Pulmonary dysfunction in awake rabbits was induced by i.v. infusion of a highly purified human fibrin split product [FSP] (fragment D). The dose of infused fragment D was chosen to achieve observed plasma concentrations of FSP in hospitalized patients with severe burns or trauma (about 100 .mu.g of FSP/ml of blood). Four hours after infusion, the animals displayed a clinical and pathological pattern which closely resembled post-traumatic acute respiratory distress syndrome, including hypoxia, hypocarbia, thrombocytopenia, increased pulmonary capillary permeability to albumin, interstitial edema, hypertrophy of alveolar lining cells and intra-alveolar hemorrhage. In vivo production of FSP by infusion of thrombin with induction of secondary fibrinolysis produced similar pulmonary changes, although intravascular clots and platelet aggregates were prominent. Infusion of human fibrinogen and human albumin at identical doses failed to induce pulmonary dysfunction. FSP (fragment D) alone are apparently toxic to the respiratory system and may contribute to the development of acute respiratory distress syndrome in severely traumatized or burned patients.