BACKGROUND Isoflurane-N2O anesthesia (as compared with halothane-N2O) reduces the cerebral blood flow (CBF) at which electroencephalographic changes occur in humans subjected to carotid occlusion. In contrast, no differences were seen in rats when cortical depolarization (instead of the electroencephalogram) was used as the ischemic marker during equi-MAC isoflurane-N2O and halothane-N2O anesthesia. To extend these findings, we used laser-Doppler flowmetry to continuously examine CBF (CBFLDF) and attempted to better define the relation between CBF and the time to depolarization (as a measure of the rate of energy depletion after ischemia). METHODS Cortical CBFLDF was measured in normothermic, normocarbic rats, and the cortical direct-current potential was recorded using glass microelectrodes. Animals were anesthetized with 0.75 MAC halothane or 0.75 MAC isoflurane, both in 60% N2O. After baseline recordings, both carotid arteries were occluded. Five minutes later mean arterial pressure was rapidly reduced to and held at target values of 50, 45, 40, 30 or 0 mmHg. This mean arterial pressure was maintained (and CBFLDF was continually monitored) until depolarization occurred, or for a maximum of 20 min. RESULTS CBFLDF values before and after carotid occlusion (but before hypotension) were similar in the two groups. As intended, CBFLDF decreased as postocclusion mean arterial pressure was reduced and the incidence of cortical depolarization increased. The delay until depolarization, defined as the interval between the moment CBFLDF reached 25% of the preocclusion baseline until depolarization occurred, decreased as CBFLDF was reduced. However, there were no intergroup differences except after a circulatory arrest (CBF = 0), where cortical depolarization was seen approximately 30 s later in isoflurane-N2O-anesthetized rats. CONCLUSIONS The CBF threshold for cortical depolarization as measured by laser-Doppler flowmetry did not differ significantly between halothane-N2O- and isoflurane-N2O-anesthetized rats. There were also no important differences in the times until depolarization, other than a small difference when flow = 0. If the time to depolarization is reflects the potential ischemic injury, the it is unlikely that isoflurane-N2O conveys any protective advantage relative to halothane-N2O.