It is well known that halothane causes an increase in cerebral blood flow (CBF). In this study the effects of halothane, enflurane, and isoflurane on regional cerebral blood flow (rCBF) in humans were determined in the presence of 70% N2O at a combined MAC concentration of 1.5. CBF was determined in 24 patients from the washout of locally applied133Xenon with the use of an external scintillation. All 24 patients (control n = 6, halothane n = 6, enflurane n = 6, and isoflurane n = 6) were undergoing neurosurgical procedures. All patients were anesthetized with thiopental, fentanyl, droperidol, and 70% N2O in oxygen and paralyzed with pancuronium. The measurements were performed after the dura had been opened and before definitive surgery. The first measurement was done in the absence of any volatile agent, and the wash-out curve was registered for 6 min. The second measurement was done after one of the volatile agents had been added for at least 20 min and had reached a concentration of 0.58% for halothane, 1.14% for enflurane, or 1.0% for isoflurane in the expiratory gases in order to obtain about 1.5 MAC with each volatile anesthetic. The anesthetic concentrations were measured with the Engström multigas analyzer EMMA®. The physiologic variables changed very little throughout the period of observation. Body temperature, heart rate, blood pressure, PaCO2, and PaO2were stable. Ephedrine was used to maintain a stable arterial pressure. At approximately 1.5 MAC, halothane (plus N2O) increased rCBF to nearly three times (166%) the control value, while enflurane induced only a slight increase (35%) in rCBF. Isoflurane caused no increase of rCBF at approximately 1.5 MAC (−5%). The authors conclude that isoflurane may well be a better alternative than halothane or enflurane during neurosurgical operations in patients with increased intracranial pressure.