In this study we tested the hypothesis that the efficacy of L-glutamate to stimulate [3H]MK-801 binding to the NMDA receptor/channel complex is altered as a function of aging. L-Glutamate, or related excitatory amino acid (EAA), is the endogenous neurotransmitter of the NMDA receptor/channel complex. These studies examined the efficacy and potency with which L-glutamate produces receptor activation, channel opening and subsequent MK-801 binding as a function of increasing age by comparing dose-response curves (EC50 and Emax) from 6-, 12-, and 24-month-old F-344 rats. The number of NMDA receptors, as determined by [3H]MK-801 binding in the presence of a saturating concentration of L-glutamate, was reduced in the inner frontal cortex, entorhinal cortex and the lateral striatum in aged rats when compared with young adults. When a range of L-glutamate concentrations were used, differences in Emax were noted in the same brain regions in addition to several others in aged and middle-aged animals when compared with young-adult animals. No changes in EC50 values were noted in any of the brain regions at either age when compared with young-adults.