Hypertension is very common in patients with chronic renal failure and contributes to cardiovascular morbidity and mortality. Several mechanisms may contribute to hypertension in these patients, but recently a large body of evidence supports the notion that activation of the sympathetic nervous system (SNS) may play a very important role. In rats with 5/6 nephrectomy, the turnover rate of norepinephrine was increased in brain nuclei involved in the noradrenergic control of blood pressure, and dorsal rhizotomy prevented hypertension. Studies in human subjects with chronic renal failure and hypertension have also shown increased peripheral SNS activity measured my microneurography in the peroneal nerve and normalization with nephrectomy. In all, these studies indicate that renal injuries may activate renal afferent pathways that connect with integrative brain structures in SNS activity and blood pressure. We have also shown that central SNS activity is modulated by local expression of nitric oxide, which, in turn, is regulated by interleukin-1b.