We studied the immunohistochemical localization of the glutamate receptor subunits GluR1, GluR2/3, and GluR4 in brains of Down syndrome patients and of normal controls. In cerebral cortex of both the control and Down syndrome patients, weak GluR1 immunoreactivity was observed in the cytoplasm of neurons, especially pyramidal neurons, after 34 weeks of gestation. In Down syndrome patients, the staining of the neurons became more distinct after 21 years of age. After 32 years of age in Down syndrome patients, GluR1 immunoreactivity was also observed in the senile plaques, including the diffuse, primitive, and classic plaques. The immunoreactivity was observed in a cluster of several small swollen neurites in the senile plaques. GluR2/3 and GluR4 immunoreactivity was also observed in the cytoplasm of neurons, especially pyramidal neurons, after 34 weeks of gestation in controls and Down syndrome patients, but not in senile plaques. GluR4 immunoreactivity was also observed in the cell processes of astrocytes in both the normal and the Down syndrome brains. Excessive immunoreactivity of GluR1 may be involved in degeneration of neurons and the early formation of senile plaques in Down syndrome.