Temporal lobe epileptogenic foci were blindly localized in 8 patients with medically refractory unilateral complex partial seizures using noninvasive in vivo proton magnetic resonance spectroscopic imaging (1H-MRSI) with 4-ml effective voxel size. The brain proton metabolite signals in 8 matched normal controls were bilaterally symmetrical within +/- 10%. The hippocampal seizure foci had 21 +/- 5% less N-acetyl aspartate signal than the contralateral hippocampal formations (p < 0.01). The focal N-acetyl aspartate reductions were consistent with pathology findings of mesial temporal sclerosis with selective neuron loss and gliosis in the surgically resected epileptogenic foci. Proton MRSI correctly localized the seizure focus in all 8 cases. By comparison, MR imaging correctly localized 7 of 8 cases and single photon emission computed tomography correctly localized 2 of 5 cases. No lactate was detected in these interictal studies. No significant changes in choline or creatine were observed. In conclusion, 1H-MRSI is a useful tool for the noninvasive clinical assessment of intractable focal epilepsy. These preliminary results suggest that 1H-MRSI can accurately localize temporal lobe epileptogenic foci.