This report describes the effects of L-glutamate (Glu) introduced into the perilymph of scala tympani on the spontaneous and tone-evoked activity of guinea pig single primary auditory afferents. Concentrations below 2 mmol/1 were in general ineffective, while a concentration of 5 mmol/1 caused a marked decrease of the neural activity. At 2 mmol/1, roughly 60% of the Glu-perfusions were effective and produced a variety of changes. The most prominent effect was a reduction of the tone-evoked activity without a change in spontaneous rate. Indeed, in some ceils, the tone-evoked activity could be almost totally abolished without affecting the spontaneous activity. More rarely observed was a moderate, generally transient increase of the spontaneous activity which was occasionally followed by a decrease in both tone-evoked and spontaneous firing rate. The increase in firing rate was always small relative to the maximum discharge rate evoked by tone stimuli. Desensitization of the Glu-evoked response without an obvious change in the spontaneous activity was also found. In a few cells Glu caused a reduction of the discharge rate below the spontaneous firing rate during loud tone presentation. Higher Glu doses generally caused a reduction of spontaneous and tone-evoked activity without any sign of a preceding increase. Thus, the effects of Glu in the mammalian cochlea appear to be complex and on balance seem inconsistent with the effects predicted for an excitatory transmitter. The findings argue against the hypothesis that Glu is the
afferent transmitter released by inner hair-cells. However, the results do not exclude an involvement of Glu as a neuromodulator or co-transmitter.