Biochemical, histological, and physiological evidence suggest strongly that astrocytes may either defend or damage brain tissue, depending on the brain carbohydrate content preceding global ischemia (28,43). This paper will first review the concept of acidosis in ischemia and the possible role of severe, compartmentalized astrocytic acidosis in pan necrosis. Results are then presented demonstrating that astrocytes are also capable of maintaining an alkaline intracellular pH (pHi) during normoglycemic global ischemia. Mechanisms underlying depolarization-dependent astroglial alkalosis are then reviewed. Recent experiments indicate that bicarbonate (HCO3-) transport is a major mechanism by which astroglia not only alkalinize their interior but also acidify the interstitium. Maintenance of alkalosis during normoglycemic ischemia supports the hypothesis that astroglial HCO3- transport might ultimately protect neurons from excitotoxicity in ischemia without infarction (17). Inhibition of astroglial HCO3- transport may be a critical and requisite event, ultimately leading to compartmentalized astroglial acidosis and irreversible injury to all cell types.