The roles of intracellular buffers and bone mineral in the regulation of acid-base balance in mammals.

1. Regulation of intracellular and extracellular pH may conflict in their requirements for movement of acid or base. 2. Cells make a positive or a negative contribution to 'tissue buffering' of extracellular fluid (ECF), depending on their internal buffer value, on the tightness of their internal pH control by membrane mechanisms, and on the nature of the acid-base disturbance. 3. A role is suggested for electrogenic Na-HCO3 co-transport in some of the ion shifts that occur in acid-base disturbances. 4. The time course of 'tissue buffering' in nephrectomized mammals in hypercapnia is variable, and it is far from clear in intact, unanaesthetized mammals. 5. Buffering of ECF by Ca salts of bone mineral in acidosis can only be substantial if accompanied by Ca excretion; the release of HCO3 with Na and K is more significant. 6. The relative importance of cells and of bone mineral in the buffering of ECF is unclear.