Tumor necrosis factor (TNF) was measured antigenically and functionally in serum and bronchoalveolar lavage fluid (BAL) of patients with ARDS and those at high risk for ARDS. Of 22 patients with ARDS, 14 had sepsis or serious infection as the major clinical predisposition, and 10 of 20 high-risk patients had sepsis or serious infection. Mean levels of TNF in serum of patients with ARDS and high risk showed a trend toward elevation but were not significantly higher than mean serum levels in normal subjects. Mean levels of TNF in BAL of ARDS patients (242 +/- 126 pg/ml) were significantly higher than in normal subjects (9 +/- 5 pg/ml), p less than 0.05. Antigenic levels of TNF were undetectable in approximately half the patients with ARDS or the high-risk state. Levels of TNF in BAL appeared to be highest in the first day of ARDS. There appeared to be no relationship between levels of TNF in serum or BAL and subsequent mortality. However, serum levels of TNF were significantly higher in septic patients than in nonseptic patients, whereas this difference was not apparent in BAL. These results show that functional and antigenic elevations of TNF are present in BAL and perhaps in serum of patients with ARDS or with the high-risk state.