Glutamate toxicity is correlated with susceptibility to autoimmune disease. Glutamate (200 nmol) was injected intravitreally into EAE-susceptible and EAE-resistant strains of mice (C57BL/6J and BALB/c/OLA, respectively), the congenic mice C3H.SW and C3H/HeJ (differing in H-2 haplotype), and rats (Lew and F344). One week after glutamate injection, more surviving RGCs were found in mice of EAE-resistant strains (C3H/HeJ and BALB/c/OLA) than in susceptible strains (C3H.SW and C57BL/6J) (p < 0.001 in both a and b). As with the mice, significantly more RGCs were seen in the retinas of EAE-resistant rats (F344) than in the retinas of EAE-susceptible rats (Lew) (c, p < 0.001). No differences in the numbers of RGCs between susceptible and resistant strains were observed on the uninjured side in either rats or mice. ***p< 0.001; Student's t test.