The relationship between expression of the autoantigens in thymi and susceptibility to autoimmune disease was determined in the experimental autoimmune encephalomyelitis (EAE) model. In two different sets of MHC congenic strains of mice characterized by differential susceptibility to EAE, levels of expression of MBP were shown to be higher in the more resistant strain. These data raised the possibility that more central tolerance to MBP may occur in more resistant strains. Differential tolerance was then evidenced by a decrease in T cell responses to MBP 83-102 in the more resistant strains. Together, these data indicate that the list of non-MHC genes involved in susceptibility to autoimmune disease should include genes which regulate expression of autoantigens in thymi.