We used single-photon emission computed tomography (SPECT) to study postictal cerebral blood flow (CBF) in 51 patients with temporal lobe epilepsy. There were 78 seizures studied, 77 by early postictal injection of Tc-99m HMPAO (delay from seizure onset = 4.3 +/- 4.5 min) and one by ictal injection. Increased focal temporal lobe uptake, predominantly confined to the anteromesial region, was present in 83% and declined rapidly over 5 minutes. Reduced activity in the lateral temporal lobe accompanied the mesial increase in 80% of studies, extending over much of the ipsilateral hemisphere and closely associated with the degree and extent of postictal EEG slow waves. These patterns enabled correct seizure localization by blinded analysis in 69% (31/45) of the patients with a unilateral EEG focus. The remainder showed bilateral or no changes. One of six patients with bitemporal EEG foci had unilateral perfusion changes. The positive predictive value for the correct localization of a unilateral focus by postictal SPECT was 97% (31/32). Postictal CBF imaging with SPECT can be used to support noninvasive electrographic localization and may decrease the need for invasive electrode studies.