Since calcium plays a modulatory role in the activity of the sympathetic nervous system (SNS), in these studies, we have tested the hypothesis that hypercalcemia may alter renal SNS activity, and, consequently, renal function. Acute hypercalcemia was induced in Sprague-Dawley rats by infusion of calcium 30mg/kg/2h in 0.45% saline. A control group of rats received only 0.45 % saline. Two more groups of rats received either calcium or 0.45 % saline 7-10 days after total renal denervation. Calcium infusion increased serum calcium by 1.8 ± 0.23 mg/dl in rats with intact renal nerves and by 2.7 ± 0.48 mg/dl in renal denervated rats. Mean arterial pressure and inulin clearance did not change during calcium or 0.45% saline in rats with intact renal nerves. Renal sympathetic nerve activity (RSNA) decreased by 44% in rats infused with calcium, but it did not change in control animals. Calcium caused a significantly greater rise in urine volume, sodium excretion and fractional excretion of sodium than the infusion of 0.45% saline. Rats with renal denervation manifested greater baseline urine volume, sodium excretion and fractional excretion of sodium than rats with intact renal nerves. Infusion of calcium, however, caused no further rise in urine sodium excretion in these animals. α-Methyltyrosine, an inhibitor of norepinephrine (NE) synthesis, also increased natriuresis in rats. Calcium reduced by 27% the NE content in the kidney but not in the heart. Methyltyrosine, on the other hand, reduced NE content in both the heart and the kidney. These data demonstrate that acute hypercalcemia inhibits RSNA and increases diuresis and natriuresis in the absence of any change in blood pressure or in glomerular filtration ra