Neurophysiologic and local cerebral metabolic mapping techniques indicate that seizures associated with lidocaine toxicity originate in subcortical brain structures. Normally local cerebral blood flow (1-CBF) is quantitatively coupled to local cerebral metabolic rate for glucose (1-CMRg). In the present study the response of 1- CBF to a lidocaine-induced preconvulsive state (localized seizure activity in the absence of a grand mal seizure) was evaluated in rats anesthetized with 60% nitrous oxide. Lidocaine administered as a bolus (20 mg/kg) followed by an infusion (4 mg/kg) over 5.5 min resulted in progressive alteration in the electroencephalogram (EEG). L-CBF was studied with the14C-iodoantypyrine autographic method when the preconvulsive EEG pattern consisted of a repetitive spike and wave complex at a frequency of 14 ± 1 · min−1complexes, superimposed on practically isoelectric background activity. Under these conditions high doses of lidocaine significantly (P< 0.05) decreased (range –30% to –68%) 1-CBF in 71% of the 34 brain regions studied. The greatest exception to this trend for 1-CBF to decrease was observed in the limbic system wherein 1-CBF remained within control ranges in eight of the 11 structures evaluated. Qualitative comparison of lidocaine 1-CBF changes with 1-CMRgchanges obtained under similar conditions indicated a general trend for local flow and metabolism to decrease in parallel. Exceptions to this were confined to certain limbic areas (amygdala and hippocampus) in which increases in l-CMRgwere more than 100% greater than slight (P> 0.05) increases in 1-CBF. This comparison demonstrates uncoupling of local brain metabolism from blood flow during lidocaineinduced subcortical epileptoid discharges (preconvulsive state) in areas recognized to be prone to irreversible damage when seizure activity is much prolonged beyond the duration of this study.