Objective:To determine whether pulmonary lactate production in patients with acute lung injury is attributable to lung tissue hypoxia.Design:Prospective, controlled, clinical study.Setting:A multidisciplinary university intensive care unit in a general hospital.Patients:Seventy consecutive critically ill patients requiring mechanical ventilation and invasive hemodynamic monitoring. Of these patients, 18 had no acute lung injury (no ALI); 33 had acute lung injury (ALI) (Lung Injury Score [LIS] ≤2.5); and 19 had acute respiratory distress syndrome (ARDS) (LIS >2.5).Interventions:None.Measurements and Main Results:After hemodynamic measurements, lactate and pyruvate concentrations were assessed in simultaneously drawn arterial (a) and mixed venous (v) blood samples. Pulmonary lactate release was calculated as the product of transpulmonary a-v lactate difference (L[a-v]) times the cardiac index. Two indices of anaerobic metabolism of the lung, i.e., the transpulmonary a-v difference of lactate pyruvate ratio (L/P[a-v]) and excess lactate formation across the lungs (XL), were calculated. L(a-v) and pulmonary lactate release were higher in patients with ARDS than in the other groups (p< .001), and they were also higher in patients with ALI compared with patients with no ALI (p< .001). In patients with ALI and ARDS (n = 52), pulmonary lactate release correlated significantly with LIS (r2= .14,p< .01) and venous admixture (r2= .13,p< .01). When all patients were lumped together (n = 70), pulmonary lactate release directly correlated with LIS (r2= .30,p< .001), venous admixture (r2= .26,p< .001), and P(A-a)O2(r2= .14,p< .01). Neither L/P(a-v) nor XL was significantly different among the three groups.Conclusion:The lungs of patients with ALI produce lactate that is proportional to the severity of lung injury. This lactate production does not seem to be attributable to lung tissue hypoxia.