We report a three-year-old boy with Reye syndrome evaluated by 99mTc-ECD SPECT. On acute stage, 99mTc-ECD brain SPECT disclosed diffuse high uptake in the cerebral cortex in spite of normal findings on brain X-ray CT. These lesions changed to general low uptake on the chronic state and multiple high intensity areas were shown on T2 weighted MRI image. Such a change of cerebral tracer uptake was considered to reflect the neuropathological change of Reye syndrome. 99mTc-ECD SPECT was a useful modality to diagnose Reye syndrome complementary.