Local cerebral glucose utilization was examined using [14C]2-deoxyglucose autoradiography following systemic administration of the AMPA antagonists 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) and 6-(2-(1H-tetrazol-5-yl)ethyl)decahydroisoquinoline-3-carboxy lic acid (LY-293558) in conscious rats. Both NBQX (10, 30 and 100 mg/kg) and LY-293558 (10, 30 and 100 mg/kg) produced marked, anatomically widespread, dose-dependent reductions in glucose utilization throughout the brain. In none of the 50 regions investigated were elevations in glucose use observed at any dose of either agent. The reductions in glucose use were accompanied by sedation, suppression of spontaneous behaviour, and respiratory depression after NBQX (30 and 100 mg/kg) and LY-293558 (30 and 100 mg/kg) administration. The greatest reductions in glucose use after NBQX or LY-293558 occurred in primary auditory regions, limbic structures (particularly hippocampal regions and cingulate cortex), neocortex and some thalamic nuclei. However, a small number of regions were found to be insensitive to either NBQX or LY-293558, most notably the superior colliculus superficial layer which failed to display significant alterations in glucose use following any concentration of either AMPA antagonist. The anatomical pattern of altered glucose use was essentially similar following either agent although the cerebral cortex, thalamus and auditory regions were more sensitive to LY-293558 and subcortical regions more sensitive to NBQX. The anatomical pattern of glucose use alterations after AMPA receptor antagonists differs from that described previously for competitive and non-competitive NMDA receptor antagonists.