The effects of MK-801 (0.5 mg/kg i.v.), a non-competitive N-methyl-D-aspartate (NMDA) antagonist, upon local cerebral glucose utilisation were examined in conscious, lightly restrained rats and in rats anaesthetised with halothane in nitrous oxide by means of the quantitative autoradiographic [14C]-2-deoxyglucose technique. In the conscious rats, MK-801 produced a heterogenous pattern of altered cerebral glucose utilisation with significant increases being observed in 12 of the 28 regions of gray matter examined and significant decreases in 6 of the 28 regions. Pronounced increases in glucose use were observed after MK-801 in the olfactory areas and in a number of brain areas in the limbic system (e.g., hippocampus molecular layer, dentate gyrus, subicular complex, posterior cingulate cortex, and mammillary body). In the cerebral cortices, large reductions in glucose use were observed after administration of MK-801, whereas in the extrapyramidal and sensory-motor areas, glucose use remained unchanged after MK-801 administration in conscious rats. In the halothane-anaesthetised rats, the pattern of altered glucose use after MK-801 differed qualitatively and quantitatively from that observed in conscious rats. In anaesthetised rats, significant reductions in glucose use were noted after MK-801 in 10 of the 28 regions examined, with no area displaying significantly increased glucose use after administration of the drug. In halothane-anaesthetised rats, MK-801 failed to change the rates of glucose use in the olfactory areas, the hippocampus molecular layer, and the dentate gyrus.(ABSTRACT TRUNCATED AT 250 WORDS)