An automatic method for identifying hippocampal atrophy on magnetic resonance (MR) images obtained from patients with clinical evidence of temporal lobe epilepsy (TLE) is described. The method is based on the analysis of image intensity differences between patients and controls within a volume of interest (VOI) centred on the hippocampus. The core of the method is a fully automatic signal intensity-based inter-subject image registration technique. In particular, a global affine registration to a reference image is performed, followed by a local affine registration within the VOI. A mask produced by manual segmentation of the mean hippocampus for 30 control subjects enabled investigations to be restricted to a specified region of the VOI approximately corresponding to the hippocampus. Normal variations of hippocampal signal intensity were computed from images obtained for the 30 control subjects. The manual method of hippocampal volumetry, currently an important component of the pre-surgical evaluation of patients with clinical evidence of medically intractable TLE, is used to determine the lower 1st percentile limits of normal hippocampal volume. Hippocampi with volumes below this limit are defined as atrophic. We investigated whether the automatic method can correctly distinguish between 15 patients with significant hippocampal atrophy according to absolute volumes and a further 14 controls. ROC curves enabled evaluation of sensitivity and specificity in respect of an intensity threshold. 100% specificity is required when determining suitability of patients for neurosurgery, resulting in levels of 50% and 70% sensitivity in detecting atrophy in the right and left hippocampus, respectively. We propose that the method can be developed as an automatic screening procedure.