The present study examined the binding of [3H]-L-glutamate to NMDA receptors, [3H]-kainate to kainate receptors, and [3H]-AMPA to AMPA/quisqualate receptors in the brains of C57Bl and BALB/c mice as a function of increasing age. Significant decreases in binding to NMDA receptors occurred with increasing age (3 to 30 months) in a majority of cortical and hippocampal brain regions from the C57Bl and BALB/c strains of mice. Significant decreases in binding to kainate and AMPA receptors were found in the inner frontal and parietal cortices and stratum lacunosum/moleculare of CA1 in both strains. These regions also exhibited the greatest percent decline in NMDA binding sites with aging. The loss of NMDA receptors in the stratum lacunosum/moleculare of CA1 was greater in the BALB/c mice than the C57Bl strain. These results demonstrate that a few brain regions have age-associated reductions in all three ionotropic EAA receptors; however, the NMDA receptor appears to be selectively vulnerable to the aging process throughout much of the cerebral cortex and hippocampus.