The involvement of opioid neurotransmitter systems in seizure mechanisms is well documented. In previous positron emission tomography (PET) studies in patients with unilateral temporal lobe epilepsy, we have found evidence for differential regulation of the opioid-receptor subtypes. The present study extends our previous observations to δ-opioid receptors by using the δ-receptor-selective antagonist [11C]methylnatrindole ([11C]MeNTI). Paired measurements of δ- and μ-opioid receptor binding and metabolic activity were performed with PET using [11C]MeNTI and [11C]carfentanil ([11C]CFN) and [18F]fluorodeoxyglucose ([18F]FDG), respectively. Binding of [11C]MeNTI and [11C]CFN increased and [18F]FDG uptake decreased in the temporal cortex (TC) ipsilateral to the focus. Decreases in [18F]FDG uptake were more widespread regionally than were increases in opioid receptors. Increases in the δ- and μ-receptor binding showed different regional patterns. Increases in δ-receptor binding were confined to the middle aspect of the inferior TC, whereas binding of δ receptors increased in the mid-inferior TC and anterior aspect of the middle and superior TC. The increase in δ receptors suggests their anticonvulsant action, as previously shown for the δ-receptor subtype, whereas the different regional pattern of receptor alterations suggest the distinct roles of different opioid-receptor subtypes in seizure phenomena.