It has been generally accepted that acidosis results in hyperkalemia because of shifts of potassium from the intracellular to the extracellular compartment. There is ample clinical and experimental evidence, however, to support the conclusion that uncomplicated organic acidemias do not produce hyperkalemia. In acidosis associated with mineral acids (respiratory acidosis, end-stage uremic acidosis, NH4Cl-or CaCl2-induced acidosis), acidemia per se, results in predictable increases in serum potassium concentration. In acidosis associated with nonmineral organic acids (diabetic and alcoholic acidosis, lactic acidosis, methanol and the less common forms of organic acidemias secondary to methylmalonic and isovaleric acids, and ethylene glycol, paraldehyde and salicylate intoxications), serum potassium concentration usually remains within the normal range in uncomplicated cases. A number of factors, however, may be responsible for hyperkalemia in some of these patients other than the acidemia per se. These include dehydration and renal hypoperfusion, preexisting renal disease, hypercatabolism, diabetes mellitus, hypoaldosteronism, the status of potassium balance, and therapy. The mechanism(s) of this differing effect of mineral and organic acidemias on transmembrane movement of potassium remains undefined. The prevalent hypothesis, however, favors the free penetrance of the organic anion into cells without creating a gradient for the hydrogen ions and, thus, obviating the efflux of intracellular potassium. The importance of the presence of hyperkalemia in clinical states of organic acidemias is obvious. A search for the complicating factors reviewed above should be undertaken since organic acidemias per se, should not be expected to be accompanied by elevations of serum potassium concentration. Moreover, the classical teaching that the absence of hyperkalemia during severe acidosis is indicative of severe potassium deficiency, may not be universally valid in patients with uncomplicated organic acidemias.