OBJECTIVE To determine whether the occurrence of hippocampal formation (HF) volumetric asymmetry can reliably discriminate between complex partial seizures (CPSs) of a temporal lobe origin and CPSs of an extra-temporal lobe origin in a prospective study of patients with intractable CPSs (approximately 70% of patients have electrographic foci in the temporal lobe [HF volumetric asymmetry on magnetic resonance imaging scans has been shown to lateralize such foci reliably)]. METHODS We examined HF volumetrics on magnetic resonance imaging scans that were acquired with a 1-T magnetic resonance imaging scanner (Siemens Magnetom, Siemens Medical Systems, Iselin, NJ) by using magnetization-prepared rapid gradient echo three-dimensional sequences (producing a gapless series of high-contrast 1.25-mm images). These data were compared with ictal, interictal, invasive, and noninvasive videoelectroencephalographic monitoring data, functional imaging data, and outcome data to define each patient's type of epilepsy. METHODS Forty-one patients were recruited from a tertiary university comprehensive epilepsy program, and 22 control subjects were recruited from the neurologically normal university community. RESULTS Among the control subjects, the difference in HF volumetrics (right-left HF volumetrics) was + 0.085 +/- 0.253 cm3. Of the 41 patients, 25 had temporal lobe epilepsy. When we set the upper limit of normal at the mean +/- 3 SDs, all patients beyond the upper limit had CPSs of a temporal lobe origin. Of the patients with temporal lobe epilepsy, only three fell within normal limits. No patient with CPSs of an extratemporal lobe origin fell beyond the upper limit. CONCLUSIONS The presence of significant HF volumetric asymmetry makes it highly unlikely that a patient's CPSs are of an extratemporal lobe origin.