The possible contribution of metabolites of arachidonic acid to the increased permeability of the alveolar-capillary barrier in the adult respiratory distress syndrome was examined by quantifying the pulmonary edema fluid concentrations of lipoxygenase and cyclooxygenase products. The concentration of leukotriene D4 in pulmonary edema fluid of 10 patients with the adult respiratory distress syndrome (18.5 +/- 6.8 pmol/ml; mean +/- SD), assessed by specific radioimmunoassay after isolation of the mediator, was significantly higher (P less than 0.001) than that of five patients with cardiogenic pulmonary edema (4.4 +/- 1.1 pmol/ml). The concentrations of leukotrienes B4 and C4, prostaglandin E2, and thromboxane B2 in edema fluid were not significantly different in the adult respiratory distress syndrome patients than in the other subjects with pulmonary edema. The edema fluid concentration of leukotriene D4 correlated with the ratio of edema fluid to plasma concentrations of albumin (r = 0.64). Leukotriene D4 thus may contribute to the permeability defect which allows an accumulation of protein-rich alveolar fluid in the adult respiratory distress syndrome.