Although changes in cerebral blood flow (CBF) and the electroencephalogram (EEG) have been reported with nitrous oxide (N2O) administration, the interaction of these parameters is unclear. The purpose of this study was to measure CBF and EEG during N2O administration in eight patients. A craniotomy was performed and CBF was measured in major brain arteries using a transit time Doppler flowmeter. EEG was recorded bilaterally from frontooccipital leads. Power spectrum analysis was performed on the EEG and power for delta, theta, alpha, and beta frequency bands analyzed over time. Arterial blood pressure was recorded continuously. N2O (66%) was added to the inspired gases during isoflurane anesthesia (0.8% end tidal) under hypocapnic (Paco2 = 29 mm Hg) and normocapnic conditions (Paco2 = 39 mm Hg). During hypocapnia, N2O administration decreased alpha EEG activity and increased delta activity but did not change CBF. During normacapnia, N2O produced similar but greater changes in EEG and increased CBF 39%. In three patients, the isoflurane concentration was increased to 1.6% end tidal during normocapnia. N2O administration in these patients also enhanced delta EEG activity and increased CBF. The slowing of EEG activity with N2O is temporally related to increases in CBF during normocapnia. Hypocapnia abolished the increase in CBF during N2O and attenuated the shift of EEG to delta activity.