We present a prospective study, designed to evaluate surfactant abnormalities in severely injured patients during the course of post-traumatic pulmonary dysfunction. Serially obtained bronchoalveolar lavage fluids from noncontused lung areas (in total, 132 samples from 17 patients) were analyzed for alveolar phospholipid composition and surfactant function in vitro during the first 14 days after trauma. The data were compared with those of 29 lavage samples obtained from 10 healthy control subjects and correlated to severity of respiratory failure. In the traumatized patients, the total lavage phospholipid content was unchanged, but there was a progressive decrease in the relative amounts of phosphatidylcholine (%PC) and phosphatidylglycerol and an increase in phosphatidylinositol, phosphatidylethanolamine, and sphingomyelin. These alterations were paralleled by a marked decrease in the hysteresis area of the surface tension isotherm. The decrease in %PC and reduction of hysteresis area were significantly correlated. The alterations in alveolar phospholipid composition and in vitro surfactant function were more pronounced in patients with severe respiratory failure. There was a significant inverse correlation between severity of respiratory dysfunction and %PC or hysteresis area for all traumatized patients. Protein leakage into the alveolar space was significantly higher in patients with severe respiratory failure and appeared to precede surfactant abnormalities in such patients. The neutrophil content in the alveolar space was markedly increased in all patients with multiple injuries however, no significant correlation with the noted alterations in alveolar phospholipid composition or surfactant function was found. We concluded that surfactant abnormalities occur during the course of post-traumatic pulmonary dysfunction and are correlated with the severity of respiratory failure.