The rapid changes in brain extracellular ion concentrations that occur with anoxia are important in understanding the pathophysiology of anoxic – ischemic brain injury. While previous studies have focused on the ionic changes that occur in gray matter areas of the brain, white matter (WM) is also damaged by anoxia. We describe the changes in extracellular K+ concentration ([K+]o) and extracellular pH (pHo) that accompany anoxia in WM, and present new results indicating that glial cells directly contribute to the observed fluctuations of these ions. Anoxia-induced changes in [K+]o and pHo were measured with ion-selective microelectrodes in the isolated rat optic nerve, a typical WM tract. To assess the contribution of glial cells, recordings were also made in optic nerves that contained only glial cells (produced by neonatal enucleation). Anoxia in WM produced less extreme changes in [K+]o and pHo than are known to occur in gray matter; in WM during anoxia, the average maximum [K+]o was 14 ± 2.9 mM (bath [K+]o = 3 mM) and the average maximum acid shift was 0.31 ± 0.07 pH unit. These extracellular ionic changes were accompanied by rapid shrinkage of extracellular space volume. The ability of optic nerve axons to conduct action potentials was lost in temporal association with the increase in [K+]o. Increasing bath glucose concentration from 10 to 20 mM resulted in a much larger acid shift during anoxia (0.58 ± 0.08 pH unit) and a smaller average increase in [K+]o (9.2 ± 2.6 mM). The increased glucose concentration presumably enhanced anaerobic metabolism, leading to extracellular lactate accumulation and a greater acid shift. More ATP would be available for operation of ion pumps, including the sodium pump, and this would result in less dramatic changes in [K+]o. The optic nerve showed significantly less irreversible damage after 60 min of anoxia in the presence of 20 mM glucose compared with 10 mM glucose. In the pure glial nerve, anoxia caused a 1.2 ± 1.1 mM increase in [K+]o and a 0.10 ± 0.04 unit decline in pHo, with time courses similar to the analogous changes in intact nerves. The small magnitude of these anoxia-induced changes in the glial preparation probably results in part from technical factors having to do with the small size of the pure glial nerves. The magnitude of the changes in the pure glial nerves was influenced by bath glucose concentration, with anoxia in 0 mM glucose producing a 1.7 ± 0.4 mM increase in [K+]o, and a 0.05 ± 0.06 unit decrease in pHo. We conclude that glial cells directly contribute to the ionic changes observed during anoxia in WM.Key words: ions, ischemia, glucose, optic nerve, compound action potential, ion-selective electrodes.