Inflammatory cells, particularly neutrophil granulocytes, have been implicated in the pathogenesis of the adult respiratory distress syndrome (ARDS). In this study, we investigated whether a relationship exists between neutrophil elastase in the plasma of multiple-trauma patients on initial hospital presentation and the subsequent development of lung injury and ARDS. Sixty-one multiple-trauma patients were enrolled prospectively. Neutrophil elastase was measured by a specific radioimmunoassay, and analysis was performed by nonparametric statistical methods. A highly significantly elevated plasma elastase level was found in patients who progressed to ARDS (median 217 ng/ml, range 127 to 480) (n = 8) compared with those who did not (median 117 ng/ml, range 21.4 to 685) (n = 53) (p = 0.009). Significant correlation was found between initial elastase values and subsequent requirement for mechanical ventilation (p = 0.01), lowest arterial oxygen saturation/oxygen supplementation recorded (p = 0.003), and organ failure score (p = 0.006). This study shows that within minutes of the initiating trauma event, there is evidence of enhanced neutrophil degranulation as manifested by elevated levels of immunoreactive neutrophil elastase in the peripheral blood. The level of this enzyme correlates with the degree of subsequent lung injury and ARDS. These findings reinforce the importance of neutrophils and their secretory products in early ARDS disease pathogenesis.