Increase in circulating levels of endothelin (ET), a potent vasoconstrictive and mitogenic endothelium-derived peptide, has been proposed as a marker of endothelium dysfunction in acute lung injury (ALI). In the present study, we have measured levels of immunoreactive ET (irET) by radioimmunoassay, in arterial (irETart), venous (irETven) and urine (irETur) samples obtained from 10 patients with ALI and 10 healthy volunteers. Arterovenous ratio, 24 h urine excretion and renal clearance of the peptide were calculated, to obtain indices of endogenous ET metabolism. The arterovenous ratio of irET was significantly higher in patients with ALI than in healthy volunteers (1.20 +/- 0.20 and 0.85 +/- 0.06, respectively; p < 0.05)). Twenty four hour urinary excretion of the peptide was increased in patients with ALI as compared to healthy volunteers (134.10 +/- 21.0 and 71.70 +/- 9.30 ng.24 h-1, respectively; p < 0.001). Renal clearance of irET was similar in patients with ALI and healthy volunteers, indicating that the increase in excretion as well as in arterovenous gradient observed in patients with ALI was related mainly to pulmonary abnormalities of peptide handling. Urinary excretion of endothelin might be a useful marker of endothelial dysfunction occurring in acute lung injury.