Type I and Type II adrenal steroid receptor levels were compared in the brain, pituitary and immune system of adrenalectomized rats in the presence or absence of several replacement doses of corticosterone. Six days of adrenalectomy produced an up-regulation of Type II adrenal steroid receptors in the brain and spleen. The lowest replacement dose of corticosterone (equivalent to resting levels of this hormone) blocked this Type II receptor up-regulation, while higher replacement doses of corticosterone were associated with widespread Type I and Type II adrenal steroid receptor down-regulation. However, the dose of corticosterone required for receptor down-regulation varied between tissues. Specifically, hippocampal receptors were most sensitive to corticosterone, whereas pituitary receptors were the least sensitive. All tissues examined, except the pituitary, exhibited a down-regulation of Type II receptors with a high corticosterone replacement dose which approximated acute stress levels of this hormone. In summary, physiologically relevant concentrations of corticosterone were capable of down-regulating Type I and Type II adrenal steroid receptors in multiple brain areas and peripheral immune tissues, including peripheral blood mononuclear cells. In contrast, adrenal steroid receptor levels in the pituitary were relatively insensitive to regulation by corticosterone.