Age-related changes in the contractile response to endothelin-1 and ACh were assessed in thoracic aortas isolated from 2-, 6- and 24-month-old male Fischer 344 rats. In aortic strips with an intact endothelium, the maximal contractile response to endothelin-1 decreased with development to maturity. Removal of the endothelium did not affect the contractile response to endothelin-1. Endothelin-1 did not elicit a relaxant response in phenylephrine-precontracted strips. The ACh-induced relaxation decreased in senescent rats. These results indicate that the contractile response of aortic smooth muscle to endothelin-1 decreases with age, and that the endothelial vasorelaxant factors do not contribute to this age-induced modulation.