Cyclooxygenase-2 (COX-2), an inducible isozyme of cyclooxygenase, is expressed selectively in response to various inflammatory stimuli such as lipopolysaccharide (LPS) and its expression is suppressed by the glucocorticoid dexamethasone (DEX) in numerous types of cells. However, LPS-enhanced production of prostacyclin in bovine arterial endothelial cells (BAEC) was not significantly decreased by treatment with DEX but was suppressed by selective COX-2 inhibitors. This is consistent with the finding that DEX was not effective at preventing the expression of LPS-induced COX-2 mRNA. Transient transfection analysis showed that DEX did not suppress the LPS-induced promoter activity of the 5′-flanking region of the human COX-2 gene (nucleotides −327 to +59). Since RNA blot analysis indicated low-level expression of glucocorticoid receptor (GR) mRNA in BAEC, a GR-expression vector was transfected to evaluate the role of the GR in the COX-2 promoter activity. It was found that DEX mediated the suppression of the LPS-induced COX-2 promoter activity in a dose-dependent manner. These results suggest that the DEX-mediated suppression of LPS-induced promoter activity of the COX-2 gene is modulated by expression of the GR, which will be possible to account for a unique expression pattern of the COX-2 gene in BAEC.