Local cerebral glucose utilization (LCGU) was measured, using the quantitative autoradiographic [14C]2-deoxy-D-glucose method, in 92 discrete brain regions of awake rats, at 1, 2, 3, or 4 h after administration of the serotonergic antagonist methiothepin 0.1 mg/kg IP. The drug produced a cataleptic behavior that peaked in intensity at 3 h after its administration. LCGU declined significantly in 35% of the 92 regions at one or more time points after methiothepin administration. No area of increased metabolism was found. The time-course of the decline in LCGU closely paralleled the intensity of catalepsy; the peak effect was at 3 h, when LCGU was significantly reduced in 32% of the regions examined (mean decline for all regions was 15%). Metabolic depression after methiothepin was most notable in the forebrain, where LCGU declined in many regions of the cerebral cortex, basal ganglia, and thalamus. Most of the regions affected by methiothepin possess a substantial number of serotonin receptors, although LCGU was also reduced in a few regions not primarily involved in serotonergic neurotransmission.