Epilepsy commonly can develop among patients with brain tumors, frequently even as the presenting symptom. The molecular pathophysiology of these seizures has been elucidated with findings that both the tumoral and peritumoral microenvironments may exhibit epileptogenic phenotypes. g-aminobutyric acid (GABA) is the chief inhibitory neurotransmitter in the mammalian SNC. In neurons the regulation of chloride is mediated by NKCC1 and KCC2 co-transporters; NKCC1 intrudes Cl^-, leading to increase [Cl^-]i, while KCC2 causes an efflux of chloride. Cell membranes isolated from peritumoral tissues (~ 2–10% glioma infiltration) of patients afflicted with gliomas (IV WHO grade) have been injected into Xenopus oocytes and compared to oocytes injected with healthy cortex. Using voltage clamp recordings, we found that the GABA currents in oocytes injected with membranes from peritumoral tissues had a more depolarized GABA_A equilibrium potential (E_GABA) compared with healthy cortex. The E_GABA shift was blocked by the NKCC1 blocker bumetanide (10 mM). Since it has been reported a modulation of KCC2 by intracellular Zn²⁺, the E_GABA shift has been reverted by using the Zn²⁺ chelator TPEN. In addition Western blot analysis has been performed on membranes extracted from peritumoral tissues resected from the same patients and from cortical tissues obtained from the same healthy patients. In the peritumoral tissues we found an increase of the expression of both NKCC1 and KCC2 transporters (70% and 25% respectively) compared to healthy tissues. Our preliminary results suggest a key role of KCC2 and NKCC1 Cl^- co-transporters in tumor related epilepsy.