In vitro incubation of mouse blood eosinophils with dexamethasone (DEX) resulted in concentration- and time-dependent reduction in CD11b and CD49d cell-surface expression as detected by flow cytometry. This inhibitory effect ranged between 20 and 40% for both integrins, and it was not related to alteration of cell survival. DEX was maximally effective at 1 microM, and it was prevented by coaddition of the glucocorticoid receptor antagonist RU486 (mifepristone; 10 microM). Budesonide, hydrocortisone, and prednisolone, but not the sex steroids testosterone and progesterone, reduced CD11b and CD49d cell-surface expression to a similar extent. Subchronic treatment of mice with 1 mg/kg DEX again reduced both CD11b and CD49d expression on circulating eosinophils, without alterations in CD11b messenger RNA expression as assessed by polymerase chain reaction analysis. In contrast, membrane but not intracellular protein expression of either CD11b or CD49d was inhibited by eosinophil incubation with DEX in vitro; thus, an interference with exportation of these adhesion molecules to the cell surface is proposed as the mechanism of action of the glucocorticoid. Finally, steroid effects on integrin expression were linked to a reduced eosinophil function as indicated by a lower degree of cell chemotaxis after incubation with DEX, an effect which was again prevented by 10 microM RU486. These observations may explain part of the therapeutic efficacy displayed by glucocorticoid hormones in the clinical control of tissue eosinophilia in allergic disease conditions.