Effects of prolonged extracorporeal circulation lasting four hours on acid-base balance were studied on dogs. Following results were obtained. 1) High flow perfusion is superior to low flow in all aspects. 2) Low molecular weight dextran is effective to prevent peripheral intravascular pooling of blood resulting in steady venous return, to maintain high flow rate and normal blood pressure, and also to inhibit increase in excess lactate. Dilution rate ranging from 15 to 25 per cent is pertinent. 3) Correction of pH with either sodium bicarbonate or Tris-buffer is preferable to compensation by respiratory alkalosis. 4) Survival time of the experimental animals can be prologed by blood replacement with fresh blood at the termination of the perfusion. However, no experimental animals survived the experiment. The same was studied on patients who underwent open heart surgery. All survived the operation and the results were as follows. 1) The metabolic changes are most prominent immediately after the perfusion and a tendency to recover appears 3 hours after the procedure. The return to normal condition is accomplished later than 5 hours after the perfusion. 2) Recovery of the various factors concerning with the acid-base balance (pH, pCO(2), baseexcess, lactids, excess lactate) is delayed proportionately to the prolongation of the perfusion time.