The pathogenesis of chronic metabolic alkalosis involves two distinct physiologic derangements.First, there must be a loss of acid or gain of alkali in order to generate the alkalosis.Renal or extra-renal factors may be responsible.If the alkalosis is generated by the kidney, the net excretion of acid in the form of titratable acid and ammonia must be increased, at least transiently, to a level greater than the sum of the acid load originating from both dietary and metabolic acid production and from alkali loss into the feces.For each mEq of excess net acid excretion by the kidney, one mEq of new bicarbonate will be generated and added to the blood.The kidney is not the only source for the generation of metabolic alkalosis.Extra-renal factors, such as vomiting, special types of diarrhea, and the like, may be the source of the alkali load. The generation of alkali by either renal or extra-renal mechanisms may not be sufficient to produce sustained metabolic alkalosis.Under normal circumstances the kidney has an enormous capacity to excrete NaHCO 3 .In consequence, increased amounts of NaHCO 3 which gain access to the blood may be promptly excreted into the urine.Clearly, then, in order to maintain metabolic alkalosis, the increased amounts of bicarbonate in the glomerular filtrate must be reclaimed by a commensurate rise in tubular reabsorption.During chronic stable metabolic alkalosis, the tubular reabsorption of bicarbonate will be persistently elevated, while the net excretion of acid will have returned to a level equal to the net acid load.The present paper will be concerned with the factors involved in the generation and maintenance of metabolic alkalosis.Physiologic determinants will be explored.Clinical derangements will then be examined.