Aim: The present experiments were designed to study the changes in endothe-lium-dependent contractions with aging. Methods: The rat femoral arteries of 20-week and 1-year-old rats with and without endothelium were suspended in organ chambers to record isometric tension. The production of oxygen-derived free radicals in the endothelium was measured with 2’,7’-dichiorodihydrofluorescein diacetate (DCF) using confocal microscopy. Protein presences were determined by West blotting. Results: In the arteries from the 1-year-old rats, endothe-lium-dependent relaxations to A23187 were reduced, but the endothelium-depen-dent contractions to A23187 (in the presence of Nω-nitro-L-arginine methyl ester hydrochloride [L-NAME; an inhibitor of nitric oxide synthase]) were augmented, demonstrating endothelial dysfunction with aging. Indomethacin normalized the responses, suggesting that a cyclooxygenase (COX)-dependent contraction is prominent in aging. The endothelium-dependent contractions were also prevented by ttroban (a blocker of thromboxane-prostanoid receptors), confirming the activation of thromboxane-prostanoid receptors on vascular smooth muscle. Valeryl salicylate and NS-398 (preferential inhibitors of COX-1 and COX-2, respectively) partially reduced the response, indicating that both COX-1 and COX-2 are involved. West blotting confirmed the upregulation of both isoforms in the arteries of the 1-year-old rats. In the presence of L-NAME, A23187 increased the DCF fluores-cence in the endothelium, demonstrating that the production of oxygen-derived free radicals contributes to endothelium-dependent contractions. The activity of catalase was reduced in the arteries with endothelium of 1-year-old rats, indicating that hydrogen peroxide is the likely mediator of increased oxidative stress in the aging endothelium. Conclusion: Endothelium-dependent contractions are aug-mented with aging. Oxidative stress potentiates the response, and both COX-1 and COX-2 are involved.