This study evaluated the activity of cardiac and renal antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPX], and glutathione reductase [GR]) and whether chronic treatment with tempol, a cell membrane-permeable SOD mimetic, ameliorates the hypertension of hyperthyroidism. Two experiments were performed. In experiment I, four groups of male Wistar rats were used: control group and three groups that received thyroxine (T₄) at 10, 50 or 75 µg/rat/day. In experiment II, tempol was orally administered (18 mg/kg/day) to control and T₄-treated (75 µg/rat/day) rats. All treatments were maintained for six weeks. Body weight, tail systolic BP and heart rate were measured once a week, and direct BP, morphological, metabolic, plasma and renal variables were measured at end of experiment. Enzymatic activities were measured in renal cortex and medulla and right and left ventricles. In renal cortex, SOD activity was decreased in the T₄-75 group, and there was a dose-related increase in CAT activity and decrease in GPX and GR activities in T₄-treated groups. Activity of all antioxidant enzymes was reduced in left ventricle in T₄-50 and T4-75 groups and in right ventricle in T₄-75 group. Tempol reduced BP, plasma MDA and total urinary excretion of F₂ isoprostanes in hypertensive hyperthyroid rats but not in controls. Tempol did not improve cardiac hyperthrophy, proteinuria or creatinine clearance in hyperthyroid rats. In conclusion, the results obtained indicate that the activity of SOD, GPX and GR in renal and cardiac tissues is decreased in hyperthyroidism and that antioxidant treatment with tempol ameliorates T₄-induced hypertension.