The sulfidopeptide leukotrienes (LT) C4 and D4 have been reported to promote the formation of pulmonary edema when administered into the pulmonary circulation of laboratory animals. As a first step in the evaluation of the hypothesis that these leukotrienes participate in the edema formation of the adult respiratory distress syndrome (ARDS), we investigated whether LTC4 and LTD4 were present in the bronchoalveolar lavage (BAL) fluid of patients with ARDS compared to nonsmoker control subjects and to patients with acute respiratory failure exhibiting no radiographic evidence of widespread pulmonary infiltrates but having a clinical predisposition for developing ARDS, i.e., the "at risk" group. Bronchoscopic lavage was performed with sterile 0.9% NaCl on 32 control subjects, nine patients with ARDS, and nine patients "at risk" for ARDS. Leukotrienes were measured in BAL fluid by radioimmunoassay after methanol extraction and HPLC purification of a 20-ml aliquot of the BAL sample. LTC4 and LTD4 (mean +/- SE) increased from 1.1 +/- 0.2 and 1.2 +/- 0.5 ng/lavage in the BAL fluid of control subjects to 6.3 +/- 2.3 and 20.1 +/- 5.9 ng/lavage in patients "at risk" for ARDS and to 12.5 +/- 3.0 and 30.5 +/- 7.8 ng/lavage in patients with ARDS, respectively. The sulfidopeptide LTs correlated with BAL fluid protein content. These results suggest that increased amounts of LTs in BAL fluid are a general finding in patients with ARDS and those "at risk" for ARDS.