We developed a magnetic resonance imaging (MRI)-based technique for measuring the volume of the hippocampal formation. In this study, the relationship between volumes of the hippocampal formation and outcome (i.e., postoperative seizure control) after anterior temporal lobectomy for intractable epilepsy was analyzed in 50 consecutive patients in whom the surgical specimen did not contain an epileptogenic mass lesion. Outcome was classified as either satisfactory or unsatisfactory. A significant relationship was found between outcome and volume of the operated hippocampal formation (p = 0.012), as well as a derived volumetric measure (nonoperated minus operated volume of the hippocampal formation) (p = 0.004). The association between outcome and nonoperated volume was borderline (p = 0.057). Thirty-four (97%) of 35 patients in whom the volumetric study and electroencephalography (EEG) concordantly lateralized the seizure disorder had satisfactory postoperative seizure control. Conversely, only 7 (42%) of 12 patients in whom the volume study was nonlateralizing and 1 (33%) of 3 in whom the EEG and volume study were discordant has a satisfactory outcome. We regard our MRI-based study of hippocampal formation volume as a noninvasive surrogate for the identification of moderate or severe mesial temporal sclerosis. The technique is a useful adjunct in a multidisciplinary, preoperative epilepsy evaluation when T2-weighted MRIs do not reveal an epileptogenic mass lesion. The reasons for the usefulness of this imaging technique are: (1) It is an independent source of information on seizure lateralization, (2) it will provide information as to expected postoperative outcome, and (3) it may aid in appropriately selecting patients for invasive preoperative monitoring studies.