PURPOSE: To use proton Magnetic Resonance Spectroscopy (MRS) to measure in vivo temporal lobe GABA and glutamate plus glutamine (GLX) concentrations in patients with temporal lobe epilepsy (TLE) attributable to unilateral hippocampal sclerosis (HS) before and following anterior temporal lobe resection (ATLR). METHODS: We obtained quantitative short echo time MRS in both temporal lobes of 15 controls and 16 patients with TLE and HS, and repeat spectra in 10 patients after ATLR. We measured the concentrations of N-acetyl aspartate+N-acetyl aspartyl-glutamate (NAAt), creatine plus phosphocreatine (Cr), and glutamate+glutamine (GLX) using a metabolite-nulled sequence designed to minimize macromolecule artifact. GABA concentrations were measured using a previously described double quantum filter. RESULTS: In patients with TLE, NAAt/Cr was reduced in ipsilateral and contralateral temporal lobes. No significant variation in GLX/Cr or GABA+/Cr was evident in any group although GABA+/Cr was highest in the ipsilateral temporal lobe in TLE. After ATLR there was a trend to normalization of NAAt/Cr in the contralateral temporal lobe but no change in individual metabolite concentrations, GLX/Cr or GABA+/Cr compared to pre-surgery levels. DISCUSSION: Temporal lobe epilepsy was associated with bilateral reduction in NAAt/Cr but not significant abnormality in GABA+/Cr or GLX/Cr. Normalization of NAAt/Cr in the contralateral temporal lobe was seen following successful ATLR.