The function of subcortical nuclei in partial epilepsy was investigated using positron emission tomography (PET) to measure metabolism in the basal ganglia and thalamus. Sixteen patients undergoing surgical evaluation were studied with 18F-fluorodeoxyglucose (FDG) interictally and had intensive extracranial and intracranial electrophysiologic evaluations. Eight patients had left temporal lobe seizure foci, six had right temporal lobe foci, and two had right posterotemporal or parietal foci. The PET data were analyzed visually and quantitatively, using a multivariate analysis of variance on the quantitative data. Hypometabolism of subcortical nuclei was present ipsilateral to the cortical seizure focus. Cortical hypometabolism was noted focally in the temporal lobe in patients with left temporal lobe seizure foci, whereas patients with right temporal lobe seizure foci had diffuse hemispheric hypometabolism. We postulate that the subcortical hypometabolism is secondary to decreased efferent activity from temporal lobe structures, in particular amygdala and hippocampus, to subcortical nuclei. Diminished subcortical activity may then lead to defective regulation of cortical excitability in the temporal lobe, increasing the likelihood of seizure development and spread.