Peripheral and central sympathetic mechanisms have been shown to contribute to the development and maintenance of increased blood pressure in the one-kidney model of renal hypertension in the rat. Previous studies from our laboratory have demonstrated that the renal sympathetic nerves, in particular, contribute to the maintenance of hypertension in this model. In those studies, renal denervation, performed 2 weeks after renal artery clipping, resulted in a significant decrement in blood pressure that was associated with a decrease in peripheral sympathetic activity. To further define the role of the renal nerves in the pathogenesis of hypertension in this model, we determined the systolic blood pressure and norepinephrine and dopamine content of the hypothalamus, midbrain, pons medulla, and spinal cord at 1 week following renal denervation or sham operation of rats with early established one-kidney one clip hypertension. Age-matched uninephrectomized rats were controls. The blood pressure of denervated animals decreased significantly from 189 ± 9.21 to 151 ± 6.5 mm Hg (p< 0.001), while that of sham-operated animals did not change. Hypothalamic norepinephrine content of sham-operated animals was significantly greater than that of controls (2.24 ± 0.8 μg/g sham vs 1.84 ± 0.12 μg/g controls,p< 0.01). Renal denervation resulted in a decrease in hypothalamic norepinephrine content to control levels (1.72 ± 0.11 μg/g)- There was a significant (r = 0.65,p< 0.01) positive correlation between systolic blood pressure and hypothalamic norepinephrine content of renaldenervated and sham-operated animals. The norepinephrine content of other brain regions was not different between groups. The results suggest that the renal nerves contribute to the maintenance of hypertension in the one-kidney one clip rat by modulating central sympathetic nervous system activity. (Hypertension 4: 369–373, 1982)