It is likely that brain tissue acidosis during ischemia is associated with neuronal injury. The authors measured brain extracellular H+, PCO2 and HCO3- concentrations during an ischemic event produced by temporary occlusion of the middle or anterior cerebral arterial distributions, with a 10-minute recovery period. Patients who were to undergo craniotomy for cerebrovascular surgery were recruited for the study. A probe that measures PCO2, pH, and temperature was inserted into tissue at risk for ischemia during temporary arterial occlusion. As a control for this treatment, PaCO2 was increased 10 mm Hg in five patients over a 10-minute period. Under baseline conditions, there was no difference in arterial blood pressure, blood gas levels, or brain temperature between patients who underwent temporary arterial occlusion or those in whom hypercapnia was induced. In patients in whom hypercapnia was induced, H+, PCO2, and HCO3- concentrations increased and all values returned to baseline levels within 10 minutes. In 10 patients who underwent a median 9-minute arterial occlusion, transient ischemia was seen with an increase in tissue H+ and PCO2 levels of 100% and 60%, respectively, and a 20% decrease in HCO3-levels. After a 10-minute postischemic recovery, only PCO2 had returned to baseline levels. These results are consistent with a rapid equilibration of lactic acidosis across the cell membrane during ischemia which decreases HCO3- concentration. After ischemia, extracellular acidosis may be prolonged because of the extrusion of H+ from the cell by membrane ion exchange.