Male spontaneously hypertensive rats (SHR) have a blunted pressure-natriuresis relationship and enhanced oxidative stress compared with female SHR. Furthermore, oxidative stress contributes to abnormal renal Na + handling and renal damage in hypertension. The aim of this study was to determine whether a sex difference exists in renal inner medullary hydrogen peroxide (H2O2) levels and/or antioxidant systems in SHR and the influence of sex steroids on these systems. Thirteen-week-old intact and gonadectomized male and female SHR were placed in metabolic cages for 24-h urine collection. Renal inner medullas were isolated for antioxidant activity assays and Western blot analysis or for measurements of H 2O2 using Amplex Red. Studies verified that male SHR had greater Na+ reabsorption compared with female SHR. Male SHR had enhanced urinary excretion of H2O2 compared with female SHR. Gonadectomy decreased H2O2 excretion in males and increased H2O2 excretion in females, suggesting that testosterone stimulates total body oxidative stress and estrogen suppresses levels of total body oxidative stress. There was not a sex difference in inner medullary H2O2 levels. Male SHR had a testosterone- dependent increase in inner medullary SOD activity, and both intact and gonadectomized males had high levels of inner medullary catalase activity compared with females. The results of this study showed that there was a sexual dimorphism in Na+ handling and oxidant status. We hypothesize that there is a testosterone-sensitive increase in whole body reactive oxygen species production that results in a compensatory increase in the inner medullary antioxidant capability possibly to normalize Na+ handling. Copyright © 2007 the American Physiological Society.