In this study, technetium-99 ((99)Tc)-hexamethylpropyleneamine-oxine single-photon emission computed tomography (SPECT) was performed on 13 children with classic lissencephaly (nine with epileptic seizures, four without seizures). Focal or multifocal hypoperfusions were observed in 12 patients. The hypoperfused areas observed on SPECT scanning did not correlate with the localization of agyric-pachygyric regions in all patients. The distribution of perfusion abnormalities by SPECT and the localization of agyria-pachygyria as detected by magnetic resonance imaging did not correlate strongly. All nine patients with seizures and three of the four patients without seizures had focal or multifocal cerebral blood flow abnormalities on the SPECT scans. The presence of brain perfusion abnormalities detected by SPECT and the occurrence of epileptic seizures did not have a significant relationship. These results suggest that the role of SPECT studies in classic lissencephaly is not clearly defined. More sophisticated methods are needed to clarify the correlation between structural and functional abnormalities of patients diagnosed with lissencephaly.