In our first two experiments, we examined brain tissue pH and tensions of oxygen and carbon dioxide in dogs core cooled to 20°C. So as to evaluate the effects of 60 minutes of circulatory arrest, 120 minutes of low-flow perfusion (25 mI/kg/mm), and 120 minutes of moderate-flow perfusion (50 mi/kg/mm), all conducted with and without pulsatile assistance. We further determined the effects of blood gas strategy on the same variables with 60 minutes of circulatory arrest. In a third experiment, we directly observed microcirculation at the surface of the brain during profoundly hypothermic perfusion. In the fourth experiment, we measured cerebral blood flow, oxygen consumption, and excessive production of lactate. Profound anoxia occurred within 20 minutes of circulatory arrest, causing severe and progressive acidosis in the brain tissues along with hypercapnia. The inhalation of 5% or 7% carbon dioxide during core cooling made the brain unacceptably acidotic. The brain acidosis was mild with low flow perfusion, and slight with moderate-flow perfusion. Pulsatile assistance improved acidosis in the brain tissues at all rates of flow. It also improved the microcirculation, the patent number of arterioles and stabilized flow in bridging veins. Cerebral metabolism became aerobic without alterations in cerebral consumption of oxygen during low-flow perfusion. We recommend flow rates above 25% of normal, alpha-stat strategy, and pulsatile assistance for better protection of the brain during profound hypothermia.