Gas exchange of oxygen and carbon dioxide between plasma and hepato- splanchnic interstitial fluid is studied by sampling thoracic duct lymph, a fluid derived primarily from the liver and extrahepatic portal bed, and its individual components, hepatic and mesenteric lymph. After in-situ isolation of the liver and small bowel in the dog by extracorporeal perfusion and oxygenation, PO2, PCO2, pH and lactate/pyruvate ratio are serially determined in thoracic duct lymph and blood from the aorta, portal and hepatic veins, and correlated with blood flow and pressure, oxygen consumption and carbon dioxide production in the liver and splanchnic bed. Data thus far indicate that changes in respiratory gas tensions in mesenteric, hepatic and thoracic duct lymph provide direct information concerning alterations in exchange of oxygen and carbon dioxide in splanchnic tissues and indirect information concerning oxidative metabolism and microcirculatory dynamics in the liver and small intestine. These findings are being pursued to elucidate some of the poorly understood problems of tissue oxygenation in hypovolemic and "septic" shock and in liver and cardiac disease.