Changes in intracellular and extracellular pH may influence the vulnerability of brain tissue to anoxic or ischemic damage. In the present study, we investigated whether the increased vulnerability of aged brain tissue to anoxic damage is associated with age-related alterations in pH regulation. We obtained evidence for altered pH regulation by measuring concurrent changes in intracellular and extracellular pH before, during, and after anoxia in hippocampal slices from young adult (6-8 months old) and aged (24-27 months old) rats. We found indications of impaired pH regulation in aged hippocampal slices (a) before anoxia, as seen in a lower resting intracellular pH, (b) during anoxia, as seen in a slower decline in extracellular pH, and (c) during recovery after anoxia, as seen in a slower rate of recovery of intracellular pH. Age-related changes in pH regulation may contribute to the faster onset of anoxic depolarization in aged brain tissue during anoxia.