During brief periods of hypoxia caused by the inhalation of pure nitrogen, reversible increases in extracellular potassium activity (aK) were detected in the guinea-pig cortex with K+-selective microelectrodes. The increases in aK produced by varying intensities of hypoxia were inversely related to the availability of O2 measured simultaneously in brain tissue with a [Formula: see text] electrode. They were associated with an increased negativity of the potential recorded between the reference electrode and ground, which is presumed to reflect depolarization of cortical elements such as glia and presynaptic terminals. When the inspired O2 concentration was raised from 21 to 100% small decreases in extracellular aK were sometimes observed.