Dendritic cells (DCs) are extremely versatile antigen-presenting cells involved in the initiation of both inate and adaptive immunity. Glucocorticoids are widely used as anti-inflammatory and immunosuppressive agents. Glucocorticoids inhibit the differentiation of immature DCs from myeloid precursors and block terminal maturation in response to microbial products and other signals. In our experiments incubation of mouse DCs with dexamethason (Dex, 10 nM, 12 h) resulted in a blunted activation of DCs by lipopolysacharide (LPS, 100 ng/ml), as assessed by reduced abundance of costimulatory molecule CD86 and reduced production of cytokines such as IL12p70 and TNF-a. Moreover, upon stimulation with LPS, DCs normally respond with a fast increase of cytosolic Ca²⁺ concentration, an event important for DC functions, such as maturation, phagocytosis, migration and cytokine production. In the present study we showed that incubation of DCs with Dex resulted in a marked inhibition of LPS-induced Ca²⁺ increase. By combination of Ca²⁺ imaging and patch-clamp technique, we demonstrated dramatic upregulation of Na⁺/Ca²⁺ exchangers by Dex. In conclusion, the effect of Dex on Ca²⁺ signaling could at least partially be due to an enhanced activity of Na⁺/Ca²⁺ exchangers and thus, enhanced extrusion of Ca²⁺ in DCs.