The hippocampus is a major structure of interest affected by temporal lobe epilepsy (TLE). Region of interest (ROI)-based analysis has traditionally been used to study hippocampal involvement in TLE, although spatial variation of structural and functional pathology have been known to exist within the ROI. In this article, structure-specific analysis (Yushkevich et al. (2007) Neuroimage 35:1516???1530) is applied to the study of both structure and function in TLE patients. This methodology takes into account information about the spatial correspondence of voxels within ROIs on left and right sides of the same subject as well as between subjects. Hippocampal thickness is studied as a measure of structural integrity, and functional activation in a functional magnetic resonance imaging (fMRI) experiment in which subjects performed a memory encoding task is studied as a measure of functional integrity. Pronounced disease-related decrease in thickness is found in posterior and anterior hippocampus. A region in the body also shows increased thickness in patients' healthy hippocampi compared with controls. Functional activation in diseased hippocampi is reduced in the body region compared to controls, whereas a region in the tail showing greater right-lateralized activation in controls also shows greater activation in healthy hippocampi compared with the diseased side in patients. Summary measurements generated by integrating quantities of interest over the entire hippocampus can also be used, as is done in conventional ROI analysis. ?? 2009 Wiley-Liss, Inc.