In other systems such as the hypothalamus and hippocampus, it has been shown that cells postsynaptic with respect to glutamatergic inputs degenerate when exposed to large doses of glutamate ('glutamate neurotoxicity'). Studies show that large doses of glutamate administered intraperitoneally are toxic to spiral ganglion cells in the inner ear of the rat. The present study investigated whether similar levels of glutamate cause alterations in the neurons of the cochlear nuclei. Specifically, the study investigated morphology and size of the cochlear nuclear complex and its subdivisions as well as the size and density of cochlear nucleus neurons following administration of glutamate. The morphological evidence indicates that glutamate caused severe anatomical alteration of the cochlear nuclei. The changes were most pronounced in the anteroventral cochlear nucleus, especially in the neurons that receive terminals of the end bulbs of Held from the cochlear nerve. This could be a direct effect of glutamate in the cochlear nuclei or secondary to degeneration of cochlear nerve fibers in the inner ear. (Copyright (c) Pergamon Press plc, 1991.)