Histocompatible Fischer 344 (F344) and Lewis (LEW) rats provide a comparative model for investigating the interactions between the nervous, endocrine and immune systems. The outbred Sprague-Dawley (SD) is the maternal strain for the inbred F344 and LEW strains. In this study we report large differences in the diurnal and stress corticosterone (CORT) profiles of these three genetically related strains: (1) F344 rats had significantly higher diurnal and stress CORT levels than SD and LEW rats; (2) in the morning, stress CORT levels of SD and F344 rats returned towards basal 1 h after cessation of the stressor, whereas stress CORT levels of LEW rats had not returned to basal by this time; and (3) in the evening, SD and F344 rats showed the expected evening rise in basal CORT levels, whereas LEW rats failed to show this rise. In light of the large differences in CORT levels, we expected to observe strain differences in absolute levels of Type I (mineralocorticoid) and Type II (glucocorticoid) adrenal steroid receptors in neural as well as immune tissue. However, we found no significant strain differences in levels of Type I receptors in the hippocampus, hypothalamus, pituitary, thymus, spleen and peripheral blood mononuclear cells. Similarly, we saw no significant strain differences in levels of Type II receptors in most of the tissues surveyed, with the notable exception that LEW rats showed higher Type II binding in the thymus, and SD rats showed small, but significantly higher Type II binding in the hippocampus. We also studied strain differences in levels of corticosteroid-binding globulin (CBG). F344 rats expressed significantly higher CBG levels than SD and LEW rats, in plasma, spleen and thymus. Future studies will investigate whether the substantial differences between strains in levels of CORT and CBG, in the context of few strain differences in post-adrenalectomy adrenal steroid receptor levels in neural and immune tissue, translate into differences in receptor occupancy/activation under resting conditions, or following stress.