Volatile anesthetic agents have profound and heterogeneous effects on global and local cerebral blood flow (I-CBF) and metabolism. The relationship between I-CBF and local cerebral glucose uptake (I-CMRg) during isoflurane anesthesia is unknown. Because these relationships might influence neuronal homeostasis during periods of cerebral ischemia of different causes, it becomes important to understand them. Accordingly, the authors evaluated the I-CBF and I-CMRgeffects of isoflurane with quantitative autoradiography in normal rats. As the dose of isoflurane increased in a stepwise fashion to 0.5, 1.0 (1.38%), 1.5, and 2.0 MAC levels, the number of structures with a significant (P < 0.05) I-CBF increase or I-CMRgdecrease became greater. At each respective MAC level I-CBF was increased in 0%, 11%, 34%, and 30%, while I-CMRgdecreased in 11%, 70%, 74%, and 81% of the structures in which autoradiographic measurements were performed. Between 1.5 MAC and 2.0 MAC the I-CMRgdecrease stabilized at about −50% to −70% of cerebral metabolic values obtained in awake control rats in association with attainment of a burst-suppression of isoelectric electroencephalogram. In contrast to these general changes, I-CMRgin two subcortical limbic system structures (dentate gyrus and interpeduncular nucleus) did not decrease, even at the highest doses of isoflurane. L-CBF was significantly (P < 0.05) increased only at the highest dose ranges (1.5–2.0 MAC) and increased from 34% to 238% in about one-third of the structures evaluated. Isoflurane anesthesia causes heterogeneous changes in I-CBF and metabolism, which are most apparent at doses at or above 1.0 MAC. Differences in I-CBF/I-CMRgratio patterns during isoflurane anesthesia suggest, at least in part, that cerebral flow and metabolic changes may proceed through unrelated regulatory mechanisms.