PURPOSE: To use proton magnetic resonance spectroscopy (MRS) to measure concentrations of gamma-aminobutyric acid (GABA) and glutamate plus glutamine (GLX) in adult patients with refractory epilepsy associated with malformations of cortical development (MCD). METHODS: We used MRS to measure N-acetyl aspartate (NAA), creatine plus phosphocreatine (Cr) and choline containing compounds (Cho), as well as GLX, and GABA. Fifteen patients with epilepsy attributable to MCD and 15 healthy controls were studied. Nine of the MCD group had heterotopia and six had polymicrogyria. Quantitative short echo time MRS [echo time (TE)=30 ms, repetition time (TR)=3000 ms] was performed in the MRI evident MCD and in the occipital lobes of the control group and the concentrations of NAA, Cr, Cho, and GLX were measured. GABA plus homocarnosine (GABA+) was measured in the same regions using a double quantum filter. RESULTS: The dominant abnormalities in the patient group were elevation of Cho and GLX and reduction in NAAt compared to the control group. The ratios GLX/NAAt and GABA+/Cr were also increased in the patient group whilst the ratio NAAt/Cr was decreased. NAAt was significantly lower in polymicrogyria than heterotopia. CONCLUSIONS: Large cortical malformations had abnormal levels of both GLX and GABA+/Cr. Low NAAt and high Cho were also observed. These results indicate that MCD show spectroscopic features of primitive tissue and abnormal metabolism of both inhibitory and excitatory neurotransmitters.