The neural mechanisms involved in learning disorders are largely unknown. We studied three-dimensional regional cerebral blood flow (rCBF) in 13 children with dysphasia and/or attention deficit disorder (ADD), using xenon 133 inhalation and emission computed tomography. The rCBF distribution was abnormal in both hemispheres in all patients, as compared with the mean CBF distribution of nine normal children. Regions of hypoperfusion and, by inference, low metabolic activity were predominantly seen in the periventricular white matter and in border zones between major arterial territories. In patients with dysphasia, parts of both perisylvian regions were hypoperfused, and object-naming tasks failed to produce an increased flow in relevant cortical regions. Patients with different dysphasic syndromes appeared to have different patterns of rCBF. All 11 patients with ADD had hypoperfusion in the white matter of the frontal lobes and seven also in the caudate nuclei region. Methylphenidate hydrochloride increased perfusion in the central region, including the mesencephalon and the basal ganglia, and decreased perfusion of motor and primary sensory cortical areas. The location of hypoperfused structures in cognitive disorders of childhood is consistent with a role for an early hypoxic-ischemic event in their origin.