Halothane is a well known cerebral vasodilator that can produce dangerous increases in intracranial pressure (CP) in certain neurosurgical patients. It has been suggested that isoflurane may be a less potent cerebral vasodilator. The authors therefore undertook a direct comparison of the effects of halothane and isoflurane on cerebral blood flow (CBF), cerebral vascular resistance (CVR), intracranial pressure, and cerebral metabolic rate for oxygen (CMR(O2)). Studies were carried out in normocarbic mechanically ventilated data using the intracarotid 133Xe injection technique to measure CBF. The effects of three doses were examined 0.5, 1.0, and 1.5 MAC, studied in the continued presence of 75% N2O. Autoregulation also was used at 1.0 MAC (plus 75% N2O) by recording CBF and CVR before and after elevation of blood pressure wih angiotensin. Both agents had similar effects on blood pressure and ICP. However, while halothane produced significant increases in CBF at all doses, with values of 61 ± 5 ml·100 g-1·min-1 (123 ± 8% of control, mean ± SE) at 1.0 MAC, isoflurane anesthesia caused no significant changes in CBF at any level, (e.g., 48 ± 8 ml·100 g-1·min-1 or 94 ± 12% of control at 1.0 MAC). Both drugs produced dose-related decreases in CVR, but the changes were greater with halothane, e.g., CVR at 1.0 MAC halothane = 1.46 ± 0.20 mmHg·ml-1·100 (47 ± 7% of control) compared with 2.23 ± 0.40 mmHg· ml-1·100 ·min (72 ± 9% of control). In addition, isoflurane produced greater decreases in CMR(O2) than did halothane, and also impaired autoregulation less. The results indicate that isoflurane possesses cerebrovascular properties that are different from halothane. These differences suggest that isoflurane may come to play an important role in future neuroanesthetic practice.