The kidney and the sympathetic nervous system importantly contribute to the development and maintenance of arterial hypertension. Clinical observations in kidney transplant recipients and renal cross-transplantation experiments in rodents provided data supporting the pathogenetic importance of the kidney in primary or “essential” hypertension. On the other hand, sympatholytic drugs effectively lower arterial pressure in hypertensive patients. Primary hypertension in experimental animals can be mitigated by renal denervation or neonatal sympathectomy. Renal transplants from spontaneously hypertensive rats (SHR) induce arterial hypertension in normotensive histocompatible recipients (renal post-transplantation hypertension). Kidney grafts from normotensive histocompatible donors normalize arterial pressure in SHR. Analysis of arterial pressure regulating systems did not provide evidence for transient volume and electrolyte retention, activation of the sympathetic nervous system, as well as increased activity of the plasma renin-angiotensin-aldosterone system during the early phase of renal post-transplantation hypertension in rats. When recipients of an SHR kidney were sympathectomized prior to induction of renal post-transplantation hypertension, the rise in arterial pressure was less than in sham-sympathectomized recipients. Neonatal sympathectomy causes a chronic arterial pressure reduction in SHR. When kidneys from neonatally sympathectomized SHR were transplanted into untreated SHR chronic arterial pressure was less than in SHR transplanted with a kidney from hydralazine-treated SHR donors. Sodium sensitivity of arterial pressure was less in recipients of kidney grafts from sympathectomized donors than in recipients of kidneys from hydralazine-treated donors. These data indicate that neonatal sympathectomy produces chronic changes in SHR renal function which contribute to arterial pressure reduction even when extrarenal sympathetic tone is restored. This finding is not specific for reduction of sympathetic activity during early life since other investigators found that ACE-inhibitor treatment in juvenile SHR gave similar results. Detailed investigation of proximal renal resistance artery function did not provide results which could explain the beneficial effect of neonatal sympathectomy. Gene expression analyses in the renal cortex and medulla with variations in NaCl intake showed a consistently reduced expression level of the NADPH oxidase subunits gp91phox and p47phox in the renal medulla of sympathectomized SHR compared to hydralazine-treated SHR with similar arterial pressure. The functional significance of this finding for renal medullary function remains to be investigated. Conclusions: 1) Elevated sympathetic activity does not mediate the development of renal post-transplantation hypertension in recipients of an SHR kidney. 2) The level of extrarenal sympathetic activity modulates the severity of renal post-transplantation hypertension. 3) Neonatal reduction of sympathetic tone induces chronic changes in renal function which contribute to long-term reduction in arterial pressure in SHR. It is suggested that the timing during ontogeny and the efficiency of blocking rather than the specific nature of the blocked “pressure system” determine the long-term effects of this type of interventions on arterial pressure in SHR.