Aims: The function of dendritic cells (DCs), antigen-presenting cells linking innate and adaptive immunity, is under the control of glucocorticoids, potent immunosuppressive hormones. Glucocorticoids influence the function of other cell types by modulating the activity of the Na+/H+ exchanger, a carrier involved in the regulation of cytosolic pH and cell volume. The present study explored whether dexamethasone influences Na+/H+ exchanger activity in DCs. Methods: The DCs were isolated from mouse bone marrow, cell volume was estimated from forward scatter in FACS analysis, cytosolic pH (pHi) utilizing BCECF fluorescence and Na+/H+ exchanger activity from the Na+ dependent realkalinization after an ammonium pulse. Results: Exposure of DCs to lipopolysacharide (LPS, 100 ng/ml) led to a gradual cytosolic acidification paralleled by a transient increase followed by a decline of Na+/H+ exchanger activity. Treatment with the glucocorticoid dexamethasone (10 nM) led to a transient decrease of pHi paralleled by a delayed sustained increase of Na+/H+ exchanger activity. Simultaneous application of LPS and dexamethasone led to a transient increase followed by a sustained decrease of Na+/H+ exchanger activity. Conclusions: The Na+/H+ exchanger in dendritic cells in regulated by both, glucocorticoids and lipopolysaccharides.