We report for the first time thatin vivotreatment with dexamethasone (DEX) reduces levels of intercellular adhesion molecule-1 (ICAM-1) expression on rat circulating unstimulated monocytes (−55%) and peritoneal macrophages (−26%). This effect was present following sub-acute (5 days) treatment with a low dose (0.1 mg/kg per day), but not after single administration of a high dose (1 mg/kg, −2 h), of the steroid. Both acute and sub-acute treatment with DEX failed to modify either basal or up-regulated CD11b expression on peripheral blood monocytes and neutrophils, elastase release from neutrophils, and β-glucuronidase release from cultured macrophages. The lack of alteration of CD11b expression on circulating leukocytes suggests that the effect of DEX on ICAM-1 expression is secondary to gene repression rather than a non-specific blockade of cell differentiation. These data promote the concept that different dose-regimens with glucocorticoids affect distinct molecular targets and indicate that clinically-related protocols of DEX may reveal new mechanism(s) of action.