Volatile anesthetic agents have profound and heterogeneous effects on global and local cerebral blood flow (l-CBF) and metabolism. The relationship between l-CBF and local cerebral glucose uptake (l-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 l-CBF and l-CMRg effects 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 less than 0.05) l-CBF increase or l-CMRg decrease became greater. At each respective MAC level l-CBF was increased in 0%, 11%, 34%, and 30%, while l-CMRg decreased in 11%, 70%, 74%, and 81% of the structures in which autoradiographic measurements were performed. Between 1.5 MAC and 2.0 MAC the l-CMRg decrease 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, l-CMRg in 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 less than 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 l-CBF and metabolism, which are most apparent at doses at or above 1.0 MAC.(ABSTRACT TRUNCATED AT 250 WORDS)