Levels of nitrite (NO2-) and nitrate (NO3-) were measured in pulmonary edema fluid and plasma from 34 patients with early acute lung injury (ALI) and 20 patients with hydrostatic pulmonary edema. Pulmonary edema fluid from patients with ALI had significantly higher levels of NO2- + NO3- compared with pulmonary edema fluid from patients with hydrostatic pulmonary edema (108 +/- 13 microM versus 66 +/- 9 microM; means +/- SEM; p < 0.05). In addition, patients with shock had higher plasma NO2- + NO3- levels than those without shock (79 +/- 11 microM versus 53 +/- 12 microM, p < 0.05). Acidemia and increased anion gap, markers of systemic hypoperfusion, were also associated with twofold higher plasma NO2- + NO3- levels (p < 0.01). Increased levels of NO2- + NO3- in edema fluid samples were associated with slower rates of alveolar fluid clearance. Nitrated pulmonary surfactant protein A (SP-A) was also detected in the edema fluid of patients with ALI after immunoprecipitation with a specific antibody against this protein. Previously, we have shown that nitration of SP-A impairs its host- defense properties. In aggregate, the results of this study indicate that reactive oxygen-nitrogen species may play a role in the pathogenesis of human ALI.