Glutamate toxicity in retinal ganglion cells has been well documented both in vitro and in vitro, and may play a role in both normal neuronal development and a variety of pathological states. Glutamate receptors are found on cell bodies and neuronal processes, both axons and dendrites. Other work has suggested that one or more of these locales may play a more pronounced role in glutamate-mediated toxicity. We now report that N-methyl-d-aspartate (NMDA) is more toxic to retinal ganglion cells with neurites. Cells without neurites were relatively unaffected by glutamate or NMDA. Cells with longer neurites or more neurite branch points were more likely to sustain NMDA-mediated neurotoxicity. These observations suggest that glutamate-mediated loss may be mediated through NMDA receptors found on neurites, rather than through a direct effect on the cell body.