The effect of a synthetic leukocyte elastase inhibitor on thrombin-induced pulmonary edema was studied in rats. The chloromethylketone human neutrophil elastase inhibitor, ICI 200,355, blunted rat leukocyte elastase activity in rat lung tissue. Administration of thrombin produced a significant increase (p < .01) in lung weight. The wet weight to dry weight ratio (WW/DW) and relative water contents were also significantly elevated (p < .01). Pretreatment with ICI 200,355 (200 micrograms/kg h-1) resulted in significant reductions (p < .05) in lung weight and a tendency to decrease WW/DW and water content compared with animals given thrombin alone. It is possible that the elastase inhibitor effectively reduced the rate of thrombin-induced pulmonary edema by attenuation of increased vascular permeability.