The effects of equipotent doses of halothane (1.05%) versus isoflurane (1.38%) anesthesia on CMR(glc) were determined autoradiographically using the 2-[14C]deoxyglucose technique in the rat. Eight anatomically standardized coronal sections were selected and digitized from the autoradiographs. Mean CMR(glc) was determined for hemispheric, neocortical, and subcortical regions at each anatomic level, and a neocortical/subcortical CMR(glc) ratio was calculated. In addition, the current CMR(glc) autoradiographs, as well as previous CBF autoradiographs obtained under identical experimental conditions were examined to characterize and compare flow/metabolism relationships for the two anesthetics. For this analysis, CBF was determined in 80 selected anatomic areas, and the values from each area were plotted against CMR(glc) values obtained from identical areas. In all major regions, mean CMR(glc) was greater with halothane than with isoflurane. The neocortical/subcortical ratio, reflecting the pattern of CMR(glc) distribution, was also greater during halothane anesthesia. This suggests that isoflurane has a disproportionate effect on neocortical metabolism resembling patterns previously seen for CBF. Analysis of CBF versus CMR(glc) plots for each anesthetic group showed two parallel lines with nearly identical slopes, but different Y intercepts. We conclude that the distribution of CMR(glc) observed during 1 MAC (minimum alveolar concentration) halothane and isoflurane anesthesia parallels the distribution of CBF. This finding supports the conclusion that flow-metabolism coupling is intact during halothane and isoflurane anesthesia, and that drug induced changes in cerebral metabolism may play an important role in determining the CBF response to that drug. Furthermore, there is evidence that, at a given level of CMR(glc), isoflurane may have greater vasodilating capabilities than halothane.