Introduction: ABCmultidrug efflux transporters such as P-glycoprotein (P-gp) are highly expressed in capillary endothelial cells and astrocytic foot processes that form the blood–brain barrier. They limit intracellular concentration of substrates by pumping them out of the cell through an active energy-dependant mechanism. An overexpression of these transporters has been associated with multidrug resistance in cancer and brain disease such as epilepsy. Epilepsy is resistant to treatment in about 1/3 of cases, but the mechanisms underlying this drug-resistance are not understood. Overexpression of P-gp in the epileptogenic brain tissue has been described to be involved in pharmacoresistance in epilepsy by actively extruding antiepileptic drugs from their target site. We used PET and the radiolabeled P-gp substrate (R)-[C-11]Verapamil (VPM) together with the thirdgeneration P-gp inhibitor Tariquidar (TQD) to evaluate P-gp function in the brain of patients with drug-resistant epilepsy.