This study was performed to determine the utility of 99mTc-hexamethylpropylenamine oxime (HMPAO) brain single photon emission computed tomography (SPECT) in evaluating patients with childhood absence epilepsy. Twenty-three patients (13 female, 10 male), aged 7 to 15 years (mean age 10.3 +/- 2.2), were studied. All patients underwent a detailed neurologic examination, interictal and ictal electroencephalography (EEG), computed tomography, and/or magnetic resonance imaging, and SPECT. The baseline study was performed during the interictal period and the activation study was performed on a separate day while the patients were having seizures provoked by hyperventilation. Their EEGs were monitored at the same time. Transaxial, sagittal, and coronal slices were obtained for both studies. The mean counts per pixel were calculated on 11 regions of interest on three representative transaxial slices. Count density was calculated for each region. Region-to-occipital cortex ratios were obtained. For each region, normalized ratios were used to obtain a side-to-side percent asymmetry index between baseline and activation studies. Visual interpretation of the baseline study showed that 10 of the 23 patients had a detectable abnormality in regional cerebral blood flow during the interictal period. These abnormalities consisted of relative hypoperfusion in the frontal lobes that could involve neighboring parietal and temporal regions. The activation study revealed that 13 of 23 patients had relative hyperperfusion in these brain regions that were relatively hypoperfused in the baseline study. These hyperperfused regions occupied larger areas than baseline hypoperfused regions. All patients had global increased perfusion in the ictal study. The side-to-side asymmetry indexes for these visually interpreted regional cerebral blood flow abnormalities ranged from 2 to 6%. The relatively consistent pattern of frontal regional cerebral blood flow alterations suggests that altered frontal lobe functions can be implicated in patients with childhood absence epilepsy.