1. Previous studies have documented that LEW/N rats exhibit an inflammatory response when challenged with a variety of stressful stimuli while histocompatible F344/N rats do not. These differences are thought to be regulated by the HPA axis. 2. In order to examine behavioral correlates of suspected differences in HPA activity in these strains, the baseline response to an open field as well as the effects of 3 micrograms/rat of CRH i.c.v. were compared across strains. 3. Significant differences in the pattern of activity in the open field, rearing, and grooming, as well as effects of CRH were found between strains. 4. The differences found are consistent with the notion that differences in endogenous CRH may form the basis for the differential susceptibility of these strains to autoimmune disease, and provide a model to study genetic determinants of CNS-immune system interactions.