An investigation of a number of factors that affect the inhibition of renal Na,K-ATPase by vanadate was performed. K is not unique in promoting inhibition by vanadate, but can be replaced by several of its congeners, the order of effectiveness being Rb > K > Cs > NH4 > Li. Although arsenate, phosphate, p-nitrophenyl phosphate and chromate all inhibit Na,K-ATPase, in that order of effectiveness, the inhibition by these anions does not depend on the presence of K or its congeners. V in the vanadyl form (V IV) is at least 12 times less effective than vanadate (V V). The reducing agents ascorbic acid and glutathione partially prevent the inhibition of Na,K-ATPase that follows the addition of vanadate; the oxidizing agents diamide and cumene hydroperoxide greatly increase inhibition of Na,K-ATPase that follows the addition of vanadyl ions. The effects of these oxidizing and reducing agents on the inhibition caused by the vanadium in Sigma ATP suggest that, in the bottle, the V is predominantly in the vanadyl form. Hydrogen peroxide completely prevents the inhibitory effects of both vanadate and vanadyl ions, probably by forming inactive peroxyvanadates. If the inhibition of renal Na,K-ATPase by vanadate has a physiological role the degree of inhibition could be controlled by altering the amount of available V by altering the fraction of V in the fully oxidized form, or by altering the local extracellular K concentration.