To assess the value of magnetic resonance imaging (MRI)-measured hippocampal volume in the detection of hippocampal sclerosis, we studied 28 patients undergoing anterior temporal lobectomy for medically intractable mesial temporal lobe epilepsy. Hippocampal volumetry and visual analysis of T2 signal change were performed using fast spin-echo T2-weighed MRI. Quantitative neuronal density measurements were performed in the resected hippocampal specimens. There was a significant correlation between MRI-measured absolute hippocampal volume (AHV) and neuronal density in CA1, CA2, and CA3 subfields (p < 0.0001, p < 0.01, and p < 0.05, respectively). Differential hippocampal volume (side-to-side volume difference) failed to detect bilateral atrophy in three patients, but the bilateral hippocampal atrophy was recognized by considering AHV in these patients. This study suggests that MRI-measured AHV can be of value in elevating patients with mesial temporal lobe epilepsy, especially when there is no side-to-side difference in hippocampal volumetry.