There is evidence that patients with adult respiratory distress syndrome are under severe oxidative stress that leads to molecular damage. Oxidative stress appears to be inherent in the disease process as well as an unfortunate complication of essential treatment with oxygen. Eight critically ill patients with an established diagnosis of adult respiratory distress syndrome requiring high inspired oxygen concentrations administered by ultra high frequency jet ventilation, were studied. Three patients survived (38%). For the group as a whole, there was evidence of increased protein damage, measured on serial plasma samples as an increase in protein carbonyls (mean +/- SEM, 1.41 +/- 0.09 nmol/mg protein), compared with Intensive Care Unit (ICU) controls (1.24 +/- 0.09 nmol/mg protein), and normal healthy controls (0.940 +/- 0.04 nmol/mg protein). Protein thiol groups were decreased in the ARDS group (4.56 +/- 0.50 nmol/mg protein) compared with ICU controls (5.5 +/- 0.27 nmol/mg protein), and the normal healthy controls (6.55 +/- 0.52 nmol/mg protein). However, when ARDS patients were grouped as survivors and non-survivors, total plasma protein levels were lower in survivors (53.9 +/- 2.15 mg/ml) compared with non-survivors (78.2 +/- 4.68 mg/ml); but the protein thiol content was significantly higher (p = < 0.001) in survivors (6.24 +/- 0.09 nmol/mg protein) compared with non-survivors (3.56 +/- 0.16 nmol/mg protein). Serial plasma measurements of protein damage indicated two different patterns. Survivors had higher total plasma thiol values (protein corrected), which increased as the lung injury resolved, and failing protein carbonyl values. By contrast, non-survivors had low and failing protein thiols often accompanying rising carbonyls.(ABSTRACT TRUNCATED AT 250 WORDS)