The objective of this study was to examine the effect of NG-monomethyl-L-arginine (L-NMMA) on phosphate excretion in the presence and absence of parathyroid hormone (PTH). Renal clearances were obtained before and during infusion of L-NMMA (15 mg/kg bolus and 500 micrograms.kg-1.min-1 infusion) in Sprague-Dawley rats with intact parathyroid glands (n = 6), in thyroparathyroidectomized (TPTX) rats receiving a constant infusion of PTH-(1-34) (0.01-0.03 U.kg-1.min-1) (n = 11) throughout the experiment, or in TPTX rats, that received an acute infusion of PTH-(1-34) (33 U/kg bolus and 1 U.kg-1.min-1 infusion) after L-NMMA infusion alone (n = 7). In rats with intact parathyroid glands, L-NMMA increased the fractional excretions of phosphate (FEPi) and sodium (FENa) and mean arterial pressure (MAP) (delta 8.6 +/- 1.5%, delta 0.62 +/- 0.1%, and delta 26.7 +/- 4.9 mmHg, respectively; P < 0.05). In TPTX rats receiving a constant infusion of PTH, L-NMMA again increased FEPi, FENa, and MAP (delta 9.5 +/- 3.6%, delta 1.1 +/- 0.4%, and delta 28.4 +/- 4.5 mmHg, respectively; P < 0.05). However, in TPTX rats, L-NMMA alone did not increase FEPi (delta 0.9 +/- 0.3%), whereas the subsequent infusion of PTH with L-NMMA increased FEPi (delta 15.6 +/- 3.1%; P < 0.05). In an additional group of intact and TPTX rats, the fractional excretion of lithium (FELi) was measured as an index of proximal reabsorption. L-NMMA increased FELi in intact rats (delta 13.2 +/- 2.6%; P < 0.05), but not in TPTX rats (delta 4.2 +/- 3.3%). In conclusion, L-NMMA increases phosphate excretion in association with increases in MAP and FENa, and this phosphaturic effect is dependent on the presence of PTH.