The structure and distribution of non-N-methyl-D-aspartate glutamate receptors in the rat brain were studied using subunit-specific antibodies that recognize the receptor subunit GluR1. The GluR1 protein, a 106-kDa glycoprotein, appears predominantly in synaptic plasma membranes, where it is highly enriched in the postsynaptic densities. When synaptic plasma membranes are solubilized with the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, high-affinity alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) binding and GluR1 immunoreactivity comigrate at a native Mr of 610,000. GluR1 is enriched in the hippocampus and cerebellar cortex but is present throughout the CNS. It is found on neuronal cell bodies and processes within most regions of the brain; within the cerebellum, however, it is localized to the Bergmann glia. These data suggest that the GluR1 protein is a subunit of multimeric AMPA-preferring glutamate receptors present on neurons and on specialized glia.