Fibroblast-like synoviocytes (FLS) play a major role in the pathogenesis of rheumatoid arthritis (RA). FLS isolated from patients with RA (FLS-RA) express B cell-activating factor belonging to the TNF family (BAFF), a cytokine that has been associated with the onset and progression of RA. Glucocorticoids are powerful anti-inflammatory drugs used in the treatment of RA. In the present study, we examined the effect of dexamethasone (Dex) on constitutive and TNF-alpha- and IFN-gamma-induced BAFF expression in FLS-RA. BAFF mRNA expression and soluble BAFF were determined by RT-PCR and ELISA, respectively. The results showed that constitutive BAFF mRNA expression was inhibited by Dex in a dose- and time-dependent manner. Also, Dex inhibited the secretion of BAFF in a time-dependent manner reaching 76% of inhibition 72 h after treatment. Moreover, Dex suppressed both mRNA and protein BAFF expression induced by TNF-alpha but had no effect on IFN-gamma-induced BAFF expression. In comparison with B cells cultured alone, B cells co-cultured with FLS-RA exhibited a higher survival, which was inhibited when FLS-RA were pretreated with Dex. However, the enhanced B cell survival was reestablished by the addition of rhBAFF. Therefore, Dex is a potent inhibitor of constitutive and TNF-alpha-induced BAFF expression in FLS-RA.