Hypopituitary Ames dwarf mice have low circulating GH/IGF-1 levels and they have extended longevity and exhibit many symptoms of delayed aging. To elucidate the vascular consequences of Ames dwarfism we compared endothelial O₂^•- and H₂O₂ production, mitochondrial ROS generation, expression of antioxidant enzymes and NO production in aortas of Ames dwarf and wild type control mice. In Ames dwarf aortas endothelial O₂^•- and H₂O₂ production and ROS generation by mitochondria were enhanced compared to those in vessels of wild type mice. In Ames dwarf aortas there was a less abundant expression of Mn-SOD, Cu,Zn-SOD, Gpx-1 and eNOS. NO production and acetylcholine-induced relaxation were also decreased in aortas of Ames dwarf mice. In cultured wild type mouse aortas and in human coronary arterial endothelial cells treatment with GH and IGF significantly reduced cellular O₂^•- and H₂O₂ production and ROS generation by mitochondria and up-regulated expression of Mn-SOD, Cu,Zn-SOD, Gpx-1 and eNOS. Thus, GH and IGF-1 promote anti-oxidant phenotypic changes in the endothelial cells, whereas Ames dwarfism leads to vascular oxidative stress.