1. The erythrocyte content of sodium and of potassium were measured in 231 unselected patients with hypokalaemia, and together with net ouabain-sensitive sodium efflux in patients with severe hypokalaemia, before (20 patients) and during potassium repletion (14 patients).
2. The erythrocytes of the patients with hypokalaemia compared with control subjects had on average an increase in sodium content, a decrease in potassium content and a reduction in the rate constant of ouabain-sensitive sodium efflux. All three changes had a similar curvilinear relation to the concentration of potassium in plasma with relatively little change in the measured variable unless the plasma potassium was very low.
3. There was a similar curvilinear relation between the final sodium and potassium content of normal erythrocytes and the potassium concentration of the medium in which they were incubated for 48 h in vitro.
4. These results suggest that the changes in the sodium and potassium content of erythrocytes in hypokalaemia are due to a direct inhibiting effect of the hypokalaemia on the activity of the sodium pump.
5. In many patients with hypokalaemia of moderate degree the increase in erythrocyte sodium content was less than expected from the effect in vitro of a low extracellular potassium concentration. This finding suggests that a compensatory change, presumably an increase in the number of sodium pumps, is a common event even in moderate hypokalaemia.