Brain extracellular potassium activity, recorded by a potassium-selective microelectrode technique, was studied in 27 anesthetized, paralyzed cats during hypoxia. Potassium activity remained essentially constant until the arterial pO2 decreased to 20 to 23 mm Hg, provided that the mean arterial blood pressure remained above 100 to 110 mm Hg. If the blood pressure was allowed to decrease during hypoxia, even to the 70 to 100 mm Hg range, the associated increases in potassium activity were accentuated, often to levels > 20 mEq per liter. The electrocorticogram regularly became isoelectric by the time the potassium activity reached 6 to 10 mEq per liter. Elevations of the blood pressure with epinephrine injections reversed both the increases in potassium activity and the electrocorticogram flattening. Extracellular potassium homeostasis during hypoxia appears to depend on the maintenance of a normal arterial perfusion pressure.