The experimental purpose of this investigation was to determine whether the efficacy of glutamate, N-methyl-D-aspartate (NMDA) and/or GABA is related to the activity state of neurons in the cochlear nuclear complex (CN). The hypothesis tested was that changes in discharge activity produced by glutamatergic and GABAergic ligands are, or may be, greater when neurons are stimulated at moderate to high acoustic levels compared to near threshold stimulation levels, when activity levels are high or low, respectively. All neurons from which discharge rate vs. sound pressure level curves were tested during simultaneous administration of amino acids exhibited characteristics commensurate with an activity-dependent system; at high sound levels, when discharge rates were elevated relative to rates produced by low level stimuli, both glutamate-induced increments and GABA-induced decrements in discharge rate were enhanced. The relationship between discharge rate and amino acid efficacy was a uniform property of neurons sampled throughout the first two postnatal weeks of development. In adults, preliminary indications are that activity-dependent neurotransmitter efficacy is characteristic of some cells, but not others. The activity-dependent nature of endogenous amino acid neurotransmission was demonstrated through the microionophoretic administration of NMDA and GABAA selective antagonists, D-α-aminoadipate (DαAA) and 2-amino-5-phosphonovalerate (APV), and bicuculline (BIC), respectively. These results suggest that postsynaptic actions elicited by membrane receptors subserving amino acid neurotransmission within the CN are activity-dependent.