Neurophysiologic studies have demonstrated epileptoid activity during high-dose narcotic anesthesia. The authors utilized the14C-2-deoxyglucose method to evaluate the local cerebral glucose metabolism (1-CMRg) during high-dose fentanyl-induced epileptoid discharges as evaluated by electroencephalography (EEG) in ventilated rats. Fentayl was administered intravenously at two dose levels (200 μg · kg-1, n = 5; and 400 μg · kg-1, n = 8). Seven unanesthetized animals served as controls. During fentanyl administration, the EEG was characterized by the appearance of isolated high voltage (>100 μV) spike and polyspike and wave complexes at a frequency of one every 1–4 s, superimposed on a baseline of reduced frequency and voltage. Isolated ictal discharges (spike or sharp waves at a frequency of 12–20/s) rarely were superimposed upon the spike and polyspike activity.As a general trend, fentanyl administration induced a significant (P<0.05) decrease of the 1-CMRg in the majority of the 37 brain structures surveyed. A clear relationship between 1-CMRg and epileptoid activity appeared when the anatomic areas were grouped into functional systems. Cerebral metabolism was globally decreased in the visual and snesorimotor systems (53–78%), in the white matter structures (76–78%), and reticular formation (59–69%) with both fentanyl treatments. The largest deviation from this trend appeared in the limbic system. Here with both treatments, the 1-CMRg in the claustrum, septal nucleus, amygdala, and ventral areas of CA1 and CA3 of the hippocampus remained at control values. At the higher fentanyl dosage, there was a more widespread depression of 1-CMRg in the rest of the brain, while in the limbic system this effect was reversed, with the 1-CMRg returning to control values in the hippocampus (CA1), dentate gyrus, and interpeduncular nucleus.The relative hypermetabolism in limbic system structures during fentanyl-induced epileptoid activity, coupled with a significant reduction of glucose utilization in the rest of the brain, suggests a role for the limbic system in the genesis of seizure activity during fentanyl administration.