Studies to date on the influence of N2O on cerebral blood flow (CBF) and metabolism in dogs, rodents, and humans have produced conflicting results. In the present study the authors have employed techniques in the awake, freely breathing nonstressed goat that allowed the authors to 1) serially obtain rapidly frozen cerebral cortical biopsy specimens (for labile metabolite assay) and 2) measure changes in cerebral O2metabolism (CMRO2) and total and regional CBF (rCBF). Thus, with each animal utilized as its own control, the authors studied N2O effects on the above variables. Two determinations of the effects of 1 h of N2O (70% via a mask) on these variables were performed on each animal. Following introduction of N2O, PaCO2and arterial blood pressure did not change, but arterial epinephrine levels declined over the 60-min period. Total CBF increased in the first 5 min of N2O exposure, reached a maximum of 165% control at 15 min, and then decreased to 143% control at 60 min. rCBF evaluations showed that much of this CBF increase was confined to cerebral cortical structures (188–246% control at 60 min). Over the same period cortical CMRO2increased to 170% of control. No appreciable changes in the levels of high-energy phosphates or glycolytic intermediates were found at 60 min of N2O. The authors attribute the described changes solely to the presence of N2O and not to sympathoadrenal influences, altered ventilation, or anything related to the experimental preparation, and they conclude that N2O (at least in goats) is associated with a marked cerebral cortical “activation.”