Increased sympathetic nervous system activity has been demonstrated in established twokidney, one clip hypertension in the rat. To determine the importance of the renal nerves in this model of hypertension, renal denervation of the clipped kidney (n = IS), renal denotation of the nondlpped kidney (n = 14), sham operation (n = 20), or undlpping (n = 12) was carried out 6 weeks after the onset of two-kidney, one clip hypertension. Nortnotensive age- and sex-matched rats were used as controls (n » 10). Sham operation or renal denerration of the nonclipped kidney produced no change in systolic Mood pressure while renal denervation of the clipped kidney resulted in a significant decrease in systolic blood pressure (195 ± 7 to 150 ± 6 mm Hg; p < 0.01). Unclipping lowered systolic Mood pressure to normotensive levels (126 ± 5 mm Hg). Eight days after operation, plasma norepinephrine and mean arterial pressure before and after ganglionic blockade with 30 mg/kg hexamethonium bromide were measured in conscious unrestrained resting animals as indices of peripheral sympathetic nervous system activity. Plasma norepinephrine was significantly higher in hypertensive sham-operated rats (347 ± 26 pg/ml) and nondipped-kidney denervated rats (355 ± 27 pg/ml) compared to nonnotensive controls (228 ± 22 pg/ml) (p < 0.01). Both renal denervation of the clipped kidney and unclipping restored plasma norepinephrine to normal levels (215 ± 16 and 232 ± 19 pg/ml, respectively). Ganglionic blockade in hypertensive sham-operated and nondipped-kidney denervated animals resulted in a significantly greater decrease in mean arterial pressure than that which occurred in clipped-kidney denervated, undipped, or control rats. There was no difference in plasma renln activity, dipped-kidney renln activity, or blood pressure response to 250 fig SQ 20,881 administration among sham-operated, dipped-kidney deoervated, or nondipped-kidney denervated animals. The data indicate that the depressor effect of dipped kidney denervation or undipping in the two-kidney, one dip hypertensive rat is associated with a decrease in sympathetic nervous system activity. These results support the hypothesis that the afferent renal nerves contribute to the maintenance of hypertension in this model by modulating the activity of the sympathetic nervous system. © 1982 American Heart Association, Inc.