Hypertension in 5/6 nephrectomized (CRF) rats is partly related to increased activity of the sympathetic nervous system. We have previously shown a greater norepinephrine turnover rate in the posterior hypothalamic nuclei and locus coeruleus of CRF than control rats. Dorsal rhizotomy prevented the rise in blood pressure and the increase in NE turnover rate in the posterior hypothalamus and the locus coeruleus. The studies suggest that afferent impulses from the kidney to central integrative structures in the brain may be responsible for hypertension in CRF rats. To further evaluate the role of renal afferent nerves in the regulation of blood pressure, and whether renal afferent pathways integrate with the posterior hypothalamus, we studied the effects of an intrarenal injection of 50 microliters of 10% phenol on blood pressure and NE secretion from the posterior hypothalamus of Sprague-Dawley rats. Mean arterial pressure increased from 89 +/- 4.0 to 114 +/- 4.3 mm Hg in rats which received intrarenal injection of phenol, but it did not change in rats that received vehicle (95 +/- 4.3 and 89 +/- 3.6 mm Hg, respectively). Renal denervation totally prevented the increase in blood pressure caused by intrarenal injection of phenol. The secretion of NE from the posterior hypothalamus increased from 139 +/- 4.8 to 250 +/- 9.9 pg/ml (P < 0.01) in rats that received intrarenal phenol, but it did not change in rats which received vehicle or in those with renal denervation. In CRF rats NE secretion from the posterior hypothalamus was greater than in control and CRF rats subjected to dorsal rhizotomy. These studies show that afferent impulses from an injured kidney increase NE secretion from the posterior hypothalamus and raise blood pressure. NE secretion is higher in the posterior hypothalamus of CRF than control rats. The posterior hypothalamus appears to be an important integrative structure of the sympathetic regulation of blood pressure.