1. Whole-body intracellular pH (pH1) was measured by the 14C-labelled DMO method in twenty-four control subjects, eighteen normal subjects with induced acute metabolic alkalosis, ten normal subjects with induced acute metabolic acidosis, twelve normal subjects with chronic acidosis and in fifteen patients with chronic renal insufficiency and acidosis.

2. The change in pH1 per unit change in extracellular pH is significantly larger in acute metabolic alkalosis than in acute metabolic acidosis. In chronic metabolic acidosis, pH1 decreased in proportion to the total amount of ammonium chloride administered; pH1 was normal in patients with uraemic acidosis.

3. These observations confirm the role that tissue buffers play in the protection of the cellular environment in some forms of acidosis. When the acid load overwhelms tissue buffer capacity, pH1 becomes a function of extracellular pH.

4. Cells seem more protected from acute acidosis than from acute alkalosis.

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