Prenatal glucocorticoids are often administered to pregnant women to accelerate pulmonary maturation. We have demonstrated that administration of dexamethasone during specific periods of pregnancy in the rat causes hypertension in the offspring when they are studied as adults. The purpose of the present study was to determine if the hypertension due to prenatal dexamethasone was mediated by renal nerves. We administered dexamethasone daily for 4 days between 15th and 18th day of gestation to rats. Rats underwent bilateral renal denervation or sham operation at 6 weeks of age and the blood pressure was measured at 8 weeks of age. Prenatal dexamethasone in the sham operation group resulted in an increase in blood pressure compared to vehicle treated sham controls (134±3 mmHg vs 145±3 mmHg, p<0.05). Renal denervation did not affect blood pressure significantly in the prenatal vehicle treated control group but resulted in normalization in blood pressure in the prenatal dexamethasone group and (130±3 mmHg and 128±5 mmHg, respectively). Prenatal dexamethasone increased NHE3, NKCC2 and NCC, but not in -, - and -ENaC protein abundance compared to controls. The increase in NHE3, NKCC2 and NCC protein abundance by prenatal dexamethasone was not seen in 8 week old rats 2 weeks after renal denervation. Renal denervation did not affect NHE3, NKCC2 and NCC protein abundance in prenatal vehicle treated animals. This study is consistent with renal nerves playing a role in mediating the hypertension by prenatal programming by dexamethasone.