A technique for sampling blood from the damaged pulmonary microvasculature in patients with acute respiratory failure is described. Blood was aspirated through the distal lumen of wedged pulmonary arterial catheters in 28 critically ill patients. Successful aspiration was achieved in 88% of the attempts and 20 ml of blood drawn before sampling was optimal for clearing mixed venous precapillary blood. The blood gas values obtained were classified as “capillary” when the wedge (w) Po2 > Pao2 and Pwco2 < Paco7 (17 patients, 61%); “mixed venous” when Pwo2 and Pwco2 were equal to values obtained from the main pulmonary artery (5 patients, 18%); and “mixed source” when intermediate Pwo2 and Pwco2 were noted, i.e., Pao2 > Pwo2 > Pvo2 and Pwco2 variably > or < Paco2 (6 patients, 21%). When mixed venous samples are eliminated, microvascular sampling can be assumed in 82% of the successful aspirations.