We performed serial measurements of plasma endothelin-1 and cytokine levels (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) in 23 children with severe acute respiratory distress syndrome during their first 7 days of disease. We report plasma endothelin-1 and interleukin-6 levels are increased in patients with acute respiratory distress syndrome, and that plasma endothelin-1 levels are significantly greater early in the clinical course of nonsurvivors than survivors. We conclude that plasma endothelin-1 levels are markedly increased in children with severe acute respiratory distress syndrome and speculate that high levels may serve as an early marker of poor outcome.