In an effort to understand the role of endogenous corticosterone production on the induction of experimental allergic encephalomyelitis (EAE) in rats, experiments in our study were performed using inbred rat strains that differ in basal corticosterone levels. Levels of corticosterone in serum samples were determined for LEW, WF, LER, and PVG rats, all of which had significantly lower corticosterone levels than BN or F344 rats. However, despite the twofold interstrain differences in basal concentrations, all animals tested showed considerable increases in corticosterone levels after being stressed by anesthesia. A series of determinations of steroid levels was made for LEW and BN rats during the postinflammatory periods of EAE induction; as expected, BN rats (EAE resistant) showed no change from their high basal levels, whereas LEW (EAE susceptible) showed consistent and long-lasting twofold increases in their circulating levels of corticosterone during the inflammatory process. Because the high corticosterone phenotype may be causally related to EAE resistance, [(BN×LEW)×BN]F1 backcross rats were tested for the possible coinheritance of the high corticosterone phenotype and EAE resistance. Contrary to the expectation of genetic linkage, our results demonstrate no correlation between the two genetic traits in this rat strain combination. © 1991 Academic Press, Inc.