Acute kidney injury (AKI) is a leading cause of morbidity and mortality, and men are more prone to AKI than women implicating androgens as a causative factor whereas estrogens have been thought to be protective. In women with hyperandrogenemia, a consequence of polycystic ovary syndrome (PCOS), it is not clear if they remain protected from AKI. In male rats exposed to renal ischemia (30 min, bilaterally), plasma testosterone levels drop, and infusion of testosterone propionate (20 μg/kg iv over 10 min) within 3 hrs of reperfusion protected the rats from elevated levels of plasma creatinine and renal injury. Blockade of the nitric oxide pathway prevents testosterone infusion from being protective in males, suggesting that androgens may be eliciting a vasodilator effect mediated by the NO system to cause protection. Blockade of the androgen receptor with flutamide has no effect on the testosterone-mediated protection from renal injury after renal ischemia-reperfusion (I/R), suggesting that testosterone is not working through the androgen receptor. Using an established female rat model of PCOS, we tested the hypothesis that chronic hyperandrogenemia in females increases the risk of I/R-induced AKI compared to placebo controls. Female SD rats were implanted with dihydrotestosterone (DHT, 7.5mg/90d) or placebo pellets beginning at 6 wks of age; pellets were changed every 85 d. At 6-7 mos of age, female rats were subjected to sham or renal I/R with bilateral clamping of renal vessels (30 min). I/R increased plasma creatinine to a higher level in DHT treated females than in sham controls. Pre-treatment with flutamide for three days prior to I/R had no effect on the plasma creatinine in the DHT treated females. These data show that exposure to chronic low levels of androgens in females causes significantly greater renal injury with I/R AKI than in sham controls, but the renal injury is independent of the androgen receptor, suggesting other mechanisms may be contributing to the higher level of renal injury after I/R AKI in females. The data also suggest that women with PCOS may have higher prevalence of AKI than do age-matched normal women.