Studies were undertaken to characterize the renal responses to acute unilateral renal denervation and chronic bilateral denervated kidneys after cholinergic stimulation of the anterior part of the lateral hypothalamus. Denervation was produced in anesthetized and conscious nondiuretic rats by application of phenol to the renal artery. Studies were also performed in sham denervated rats. Whole kidney function in anesthetized animals showed a significant increase of fractional sodium excretion (0.7 +/- 0.1 to 1.7 +/- 0.4%, P less than 0.01) both in the denervated and in the innervated kidney (0.09 +/- 0.02 to 1.1 +/- 0.2%, P less than 0.005) after carbachol injection into the LHA, whereas the percentage of filtered potassium excreted increased only in the innervated kidney (11.4 +/- 1.3 to 16.3 +/- 1.1%, P less than 0.01). Similarly, in conscious rats, fractional sodium excretion increased after cholinergic stimulation in animals having denervated kidneys (2.1 +/- 0.1 vs 3.6 +/- 0.2%, P less than 0.005). Fractional potassium excretion also increased both in rats with sham-denervated and denervated kidney. There was an acute elevation in mean arterial blood pressure and glomerular filtration rate (GFR) during the first 20-min after carbachol injection. Sodium excretion was statistically significant during the three 20-min collections of the experimental period. This suggests that the natriuresis is not associated with increased arterial pressure, GFR or renal plasma flow. Our results indicate that natriuresis occurs even in the absence of the renal nerves.