This study examined whether the anti-oxidants ascorbic acid, alpha- or gamma-tocopherol, could modify adrenocorticotrophic hormone (ACTH)-hypertension in Sprague-Dawley rats, a model associated with increased oxidative stress. Systolic blood pressure (SBP) was measured by the tail-cuff method. After four days of ascorbic acid (AA) (200 mg/kg/day drinking) or alpha-tocopherol (500 mg/kg/d i.p. or feed), rats were co-administered ACTH (0.2 mg/kg/day s.c.) or saline for 11 days (prevention studies). In reversal studies, ACTH/saline was administered for 15 days, and from day 9, alpha- or gamma-tocopherol (20 mg/kg/day) was added. ACTH increased SBP compared to saline (p < 0.05). AA or alpha-tocopherol failed to prevent and alpha- or gamma-tocopherol failed to reverse ACTH-induced hypertension. Thus, neither vitamin C (water soluble) nor E (lipid soluble) modified ACTH-induced hypertension in the rat.