We investigated the effects of glucocorticoids on group II phospholipase A2 (PLA2) expression in rat cultured smooth muscle cells. Both forskolin-induced and tumor necrosis factor (TNF)-induced PLA2 release responses were almost completely blocked by 10 and 100 nM dexamethasone, respectively, as assayed by protein blotting and PLA2 activity assays. Dexamethasone-mediated inhibition of PLA2 release appeared to be mediated by the glucocorticoid receptor. Dexamethasone at concentrations greater than 10 nM inhibited forskolin-induced elevation of the group II PLA2 mRNA level but not TNF-induced elevation. These data suggest that the mechanism mediating forskolin-induced mRNA accumulation is sensitive to glucocorticoids, but the mechanism mediating the TNF-induced accumulation is not. Inhibition of TNF-induced PLA2 release by glucocorticoids may be explained by the blocking of post-transcriptional synthesis of the group II PLA2.