To study the effect of antiepileptic drugs (AEDs) on 5-HT(1A)-receptor binding in patients with temporal lobe epilepsy. 5-HT(1A)-receptor binding, measured by positron emission tomography, is reduced in patients with temporal lobe epilepsy. Antiepileptic drugs may act on the serotonergic system, as shown in animal models, and thus affect receptor-binding measurements.We analyzed the effect of AEDs on 5-HT(1A)-receptor binding in 31 patients and 10 normal controls. Patients with structural lesions, progressive neurologic disorders, or taking other medications were excluded. None had a seizure for >or=2 days before positron emission tomography (PET). [(18)F]FCWAY PET was performed on a GE Advance scanner with continuous EEG monitoring. Functional images of the distribution volume (V) were generated. Anatomic regions of interest were applied to co-registered PET images, after correction for partial-volume effect.Patients had significantly higher [(18)F]FCWAY free fraction (f(1)) than did controls. No AED effects were observed on interictal [(18)F]FCWAY binding after correction for plasma free fraction. [(18)F]FCWAY V/f1 reduction in epileptic foci was not affected by AEDs.5-HT(1A)-receptor binding is reduced in temporal lobe epileptic foci after partial-volume correction. AED plasma free fractions should be measured when PET receptor studies are performed in patients with epilepsy.