Sodium salicylate was administered to anesthetized dogs in doses sufficient to produce concentrations in plasma comparable to those common in human salicylate toxicity. Salicylate administration increased the rates of excretion of water, sodium, and chloride in the urine. Salicylate administration also increased the rate of excretion of potassium so that its clearance often exceeded that of creatinine. This enhancement of potassium excretion was dissociated from the alkalosis that accompanies salicyate toxicity. Administration of 5% CO(2) in inspired gas did not attenuate the excretion of potassium; injection of salicylate into one renal artery caused a unilateral kaliuresis. Phosphate excretion increased progressively after administration of salicylate. On several occasions the clearance of phosphate equalled that of creatinine. Salicylate reduced renal tubular glucose reabsorption. When salicylate was injected into a renal artery, a glycosuria occurred ipsilaterally at filtered loads of glucose far below the reabsorptive capacity of the dog kidney. Salicylate administration also was associated with early elevation of glucose, phosphate, and potassium concentration in plasma. Salicylate administration reduced the content of adenosine triphosphate in the renal medulla. Salicylate was concentrated within the medulla between 1.5 and 3 times that of the cortex, a gradient equal to that for chloride.