The effects of halothane and isoflurane on regional cerebral blood flow (CBF) were studied in 18 New Zealand White rabbits anesthetized with nitrous oxide (N2O) and morphine sulfate (MS) at three different levels of Paco2.CBFwas measured using the hydrogen clearance technique. Monitored variables were intracranial pressure (ICP), central venous pressure, heart rate, mean arterial pressure, electroencephalogram, arterial blood gases, end-tidal (ET) volatile anesthetic, and ET CO2. Addition of 1 MAC halothane to the N2O/MS background anesthetic caused flow to increase significantly in all three regions studied (cortex, dorsal hippocampus, white matter) at all three levels of Paco2(low: 20–25 mmHg; normal: 35–40 mmHg; high: 50–55 mmHg). Addition of 1 MAC isoflurane to the background anesthetic caused CBF to decrease significantly in all regions during hypocapnia. During normocapnia, CBF was unchanged with the addition of 1 MAC isoflurane in all regions and during hypercapnia, CBF increased significantly only in the dorsal hippocampus following addition of 1 MAC isoflurane to the MS/ N2O background anesthetic. Volatile anesthetic administration was associated with significant, although small, increases in ICP at all Paco2levels. We conclude that 1 MAC concentrations of halothane and isoflurane have opposite effects on CBF when added to a N2O/ MS anesthetic during hypocapnia and that the effects of isoflurane on regional CBF are dependent on Paco2in rabbits under the anesthetic conditions of this experiment.