Brain pH changes during ischemia were observed by the newly established histochemical technique in Dr. Kogure's laboratory (Miami). The technique utilizes intravascular injection of neutral red as a pH indicator. Its use is based on the fact that neutral red is red in acid and yellow in alkaline pH. Thalamic infarction model in dogs was used in this experiment. The methods of producing this model by temporary occlusions of brain arteries have been published elsewhere. The animals were anesthetized with sodium thiopental, immobilized with pancronium bromide, and artificially ventilated with room air. Blood gases and blood pH were adjusted to normal. Before the experimental procedure, 3 ml/kg of a 5% saline suspension of neutral red was injected slowly into the femoral artery. After occlusions of cerebral arteries, the brain was frozen in situ by pouring liquid nitrogen into the bottomless cup. The frozen brain was mounted on a cryostat at -20 degrees C and sliced coronally in 10 micron thickness. Color differences in the serial sliced brain surface were observed. No change in the color was observed in the sham operated brains. Thirty minutes following occlusion, the color of the thalamus is reddish, and it was estimated that this area became acidotic. 1 hour following occlusion, too, the thalamus is acidotic. But 2 hour following occlusion, the color of the thalamus became yellowish, indicative of alkaline shift. From this experimental results, it is considered that the pH of ischemic brain changes dynamically, that is, ischemic brain becomes acidotic in the early stage of ischemia but with the lapse of time alkaline shift occurs.