To investigate the correlation between involvement of the CNS in motor neuron disease (MND) and neuroimaging abnormalities, we studied 18 patients with MND by single-photon emission computed tomography (SPECT) and MRI. Patients were divided into four groups according to the results of SPECT. Group 1 consisted of four patients with reduced isotope uptake in the frontal lobe, including the motor area, and in the anterior part of the temporal lobe; group 2 consisted of two patients with reduced isotope uptake in the motor area spreading to the adjacent frontal lobe; group 3 consisted of eight patients with reduced isotope uptake confined to the motor area; and group 4 consisted of four patients without reduced isotope uptake. We found dementia in group 1, borderline dementia in group 2, and no cognitive deficit in group 3 or four. MRI demonstrated enhanced T2-weighted signals along the pyramidal tract in eight patients, but this finding also existed in some control subjects. SPECT appears useful in identifying the location of cortical neuronal degeneration in patients with MND.