Studies were done on rats to determine whether thiopental loading after complete, transient, global brain ischemia causes more rapid postischemic normalization of brain tissue pH. Fifteen halothane-anesthetized rats were subjected to 16 min of complete global brain ischemia by a combination of systemic arterial hypotension (40 torr) and a high pressure (1500 torr) neck cuff. Brain tissue pH was continuously monitored for up to 2 hour postischemia with microelectrodes (tip diameters of one to two micrometers) inserted about 500 micrometers into the parietal cortex. During ischemia, brain pH fell rapidly within the first 5 min from 7.0 to 6.2 and changed little thereafter. With restoration of arterial pressure and deflation of the neck cuff, pH did not immediately begin to rise back towards normal. Instead, after a few minutes, it transiently fell to even lower values before beginning to increase indicating increased tissue lactic acidosis when the brain is resaturated with glucose upon reperfusion. Beginning at 5 min postischemia, 7 of the 15 rats were infused with thiopental (90 mg/kg, IV over 60 min). At 30 min postischemia, brain tissue pH was similar in both groups and by 60 min, back to preischemic values. We conclude that thiopental loading postischemia does not improve normalization of brain pH. The transient decrease in brain pH with reperfusion is discussed.