The prefrontal cortex is asymmetric in both structure and function. In normal subjects, the right prefrontal cortex is activated more than the left during response inhibition. Patients with attention deficit hyperactivity disorder (ADHD) have impaired response inhibition and altered structural interhemispheric asymmetry. This study was conducted to examine the functional interhemispheric asymmetry during response inhibition in children with ADHD. Subjects were divided into three groups according to the level of motor hyperactivity. Blood flow tracer (99m)Tc-ethyl cysteinate dimer was injected while subjects were performing a response inhibition task (RIT), followed by single photon emission computerized tomography (SPECT). After three-dimensional reconstruction, filtering and smoothing, individual scans were morphed to a template. Three average group images were created from individual scans. Each average group image was subtracted voxel-by-voxel from its mirror image to compare the regional cerebral blood flow (rCBF) in the right and left cerebral hemispheres, yielding images of significant interhemispheric rCBF asymmetry. The severe hyperactivity group exhibited most prefrontal left>right rCBF asymmetry and left>right occipitoparietal asymmetry. Reversal of functional prefrontal asymmetry in boys with severe motor hyperactivity supports the hypothesis of right prefrontal cortex dysfunction in ADHD.