OBJECTIVE To test a hypothesis predicting that isoflurane would interfere with cerebrovascular autoregulation in horses and to evaluate whether increased mean arterial blood pressure (MAP) would increase cerebral blood flow and intracranial pressure (ICP) during isoflurane anesthesia. METHODS 6 healthy adult horses. METHODS Horses were anesthetized with isoflurane at a constant end-tidal concentration sufficient to maintain MAP at 60 mm Hg. The facial, carotid, and dorsal metatarsal arteries were catheterized for blood sample collection and pressure measurements. A sub-arachnoid transducer was used to measure ICP Fluorescent microspheres were injected through a left ventricular catheter during MAP conditions of 60 mm Hg, and blood samples were collected. This process was repeated with different-colored microspheres at the same isoflurane concentration during MAP conditions of 80 and 100 mm Hg achieved with IV administration of dobutamine. Central nervous system tissue samples were obtained after euthanasia to quantify fluorescence and calculate blood flow. RESULTS Increased MAP did not increase ICP or blood flow in any of the brain tissues examined. However, values for blood flow were low for all tested brain regions except the pons and cerebellum. Spinal cord blood flow was significantly decreased at the highest MAP. CONCLUSIONS Results suggested that healthy horses autoregulate blood flow in the CNS at moderate to deep planes of isoflurane anesthesia. Nonetheless, relatively low blood flows in the brain and spinal cord of anesthetized horses may increase risks for hypoperfusion and neurologic injury.