Sodium orthovanadate (vanadate) is a powerful inhibitor of (Na+,K+) adenosine triphosphatase and exhibits widespread actions on the renal and cardiovascular systems. In the present study, the effect of vanadate on the functions of the isolated perfused rat kidney was studied. The control parameters for this preparation were: glomerular filtration rate, 225 microliter/min; urine flow, 40 microliter/min; fractional sodium reabsorption, 92%; and total peripheral resistance, 765 kilo pascals/l/min. Varying concentrations of vanadate in the perfusate (0 to 32 microM) produced a dose-dependent rise in glomerular filtration rate, urine flow, total peripheral resistance and inhibition of sodium reabsorption. At higher concentrations, vanadate was nephrotoxic. Since vanadate produces simultaneous rises in glomerular filtration rate and total peripheral resistance, a postcapillary vasoconstrictor effect for the anion is postulated. Clearance of vanadate from the perfusate was determined at various concentrations of the anion in the perfusate and the reversibility of vanadate effect on the kidney was studied. In conclusion, vanadate is a potent diuretic, natriuretic and vasoconstrictor in the isolated, perfused rat kidney and is nephrotoxic at higher dose levels.