We have examined the responses of brain endothelium from different rat strains to interferon-gamma (IFN-gamma) which induces expression of MHC class II molecules. There is a marked difference between the strains in the sensitivity of their endothelium to MHC induction. LEW and DA rats, which are susceptible to experimental allergic encephalomyelitis (EAE) can be induced to express higher levels of class II molecules than EAE-resistant strains. In both the EAE-susceptible and -resistant strains, RT-1B locus-encoded molecules occur at higher surface densities than RT-1D locus molecules. These findings support the theory that genes controlling the induction of MHC expression affect disease susceptibility.