Objective: The etiology of lung injury following cardiopulmonary bypass (CPB) is multifactorial. Our study focused on quantifying the lactate release from the lungs precipitated by extracorporeal circulation at different time points after the insult. This was complemented by an evaluation of the gas exchange at the level of the alveolar-capillary membrane. ----- Methods: Forty consecutive patients (age 61+/-11 years, EuroScore 4.7+/-2.7) undergoing CABG were prospectively analyzed. The data are presented as medians and the interquartile range. ----- Results: The pulmonary lactate release (PLR) increased from a baseline value of 0.033 (range -0.077 to 0.170) to 0.465mmol/min/m(2) (range 0.113-0.922), which was seen 6h postoperatively (P<0.001). The A-a O(2) gradient increased from 12.7 (range 8.8-15) to 39.1kPa (range 30.3-46.5) upon discontinuation of CPB (P<0.001). The systemic arterial lactate (L(S)) concentration increased from 1.22 (range 1-1.44) to 3.03mmol/l (range 2.29-4.76) 6h after surgery (P<0.001). The veno-arterial pCO(2) difference (V-A dpCO(2)) rose from 0.6 (range 0.5-0.9) to 0.9kPa (range 0.7-1) (P=0.014). The mortality in the studied group was 5% (2/40). ----- Conclusions: The lungs were found to be a significant source of lactate, and this pulmonary lactate flux was accentuated by CPB. The PLR correlated with systemic hyperlactatemia as well as the A-a O(2) gradient, and was found to be higher in patients requiring prolonged mechanical ventilatory support. The duration of CPB had a significant impact on the systemic lactate concentrations, V-A dpCO(2) and the A-a O(2) gradient, but not on the PLR.