The renal effects of sodium vanadate (Na3VO4), an inhibitor of sodium-potassium-ATPase recently shown to be a potent diuretic, were studied by using clearance and micropuncture techniques in nondiuretic anesthetized rats. Administration of 1.0 mumole of sodium vanadate (high dose) increased urine flow rate (V) from 9.8 +/- 1.4 to 17.5 +/- 4.0 microliter/min (mean +/- SEM, P < 0.025), UNaF from 1.73 +/- 0.36 to 3.05 +/- 0.65 microEq/min (P < 0.025), and FENa from 0.67 +/- 0.15 to 1.24 +/- 0.28% (P < 0.025)., No significant changes in GFR or RPF were observed. Late proximal tubular-fluid-to-plasma (F/P) inulin decreased from 2.28 +/- 0.19 to a minimum value of 1.38 +/- 0.06 (P < 0.025). Absolute water reabsorption decreased from 15.8 +/- 3.5 to 6.5 +/- 1.7 nl/min (P < 0.025) and fractional water reabsorption from 52.0 +/- 4.4 to 26.5 +/- 4.1% (P < 0.025). The injection of 0.5 mumole of sodium vanadate (low dose) resulted in no significant changes in V. Late proximal F/P inulin decreased, however, from 2.37 +/- 0.14 to a minimum value of 1.59 +/- 0.12 (P < 0.025). SNGFR remained unchanged, as did GFR and RPF. UNaV increased from 1.41 +/- 0.35 to 2.25 +/- 0.35 microEq/min (P < 0.025), and FENa rose from 0.64 +/- 0.16 to 0.91 +/- 0.15% (P < 0.025). The decrease in F/P inulin was observed in all but one animal, even in the absence of a diuretic response. The amount of fluid remaining in the lumen of the late proximal tubule was virtually the same in both low- and high-dose animals (18.9 +/- 3.0 and 19.5 +/- 3.4 nl/min, respectively). We conclude that sodium vanadate causes a decrease in superficial proximal tubule fluid and salt reabsorption. Inasmuch as the low dose does not result necessarily in a diuretic response, an increase in fluid reabsorption distal to the late proximal tubule must take place.