The initial disturbances in acid-base equilibrium and the pathways of recovery have been studied in 33 patients, predominantly infants and young children, with salicylate intoxication due either to accidental ingestion or to therapeutic overdosage. In nearly all patients there were significant reductions in the total content of carbon dioxide and in pCO2 of plasma; pH of the blood did not vary consistently: some patients were alkalotic, others were acidotic, while still others had no significant deviation in pH of the blood. Evidence was obtained in many of the patients for a mixed disturbance in acid-base equilibrium with primary disturbances in the metabolic and in the respiratory components. The nature of the component of metabolic acidosis has been analyzed by a detailed study of the anions in the serum of five patients with this disturbance. A variety of anions were present in excess: chloride, salicylate, and undetermined anion; in one patient the concentration of phosphate was also elevated. Reasons are presented suggesting that the undetermined anion fraction represents largely ketone bodies. The pathway of return to normal acid-base equilibrium was studied with six patients presenting with acid pH. The predominent tendency of this group was to recover through a point at which pH of the blood was normal or even alkaline, even though pCO2 was still low. In two patients initially presenting with acid pH, acute respiratory depression supervened after acute pulmonary edema. Respiratory depression was accompanied by a marked elevation of pCO2 and a marked fall in pH. One of these patients expired; the other was successfully ventilated by artificial means and made a full recovery. The basic actions of toxic amounts of salicylate—respiratory stimulation, changes in metabolic rate, and disturbances in the metabolism of carbohydrate, protein and fat—are reviewed. The pathogenesis of the acid-base disturbances is formulated in terms of these known actions of toxic amounts of salicylate. Several factors correlate with the particular type of disturbance which a given patient may develop and may be important as conditioning influences. These factors are age of the patient, duration of the intoxication, type of intoxication (i.e., whether accidental or the result of therapeutic over-dosage) and, perhaps, the amount of salicylate ingested.