Changes in the extracellular concentration of glutamate in the brain ([Glu]e) were monitored continuously by an enzyme-amperometric technique employing a dialysis electrode during ischemia caused by isolation of the brain tissue in rats and human patients. In the rat (n = 10), the dialysis electrode was placed in the frontal cortex and the frontal lobe was transected. A transient sharp increase in [Glu]e was frequently observed during the transection. A biphasic elevation (a rapid increase followed by a slowly continuing increase) subsequently occurred with a latent period of 1-3 min after the transection of the rat frontal lobe. In patients (n = 7), the dialysis electrode was placed in tumor-free cortical areas which were planned to be resected together with gliomas. Progressive increases in [Glu]e were observed in all of the patients as the isolation of the brain tissue progressed. A biphasic increase, similar to that seen in the rat, was identified in 2 patients in whom the cortical area surrounding the dialysis electrode was rapidly isolated. The present enzyme-amperometric technique employing a dialysis electrode appears to be useful for detecting the occurrence of potentially harmful ischemia and for securing minimal metabolic stress caused during various surgical manipulations.