1. Intracellular cation composition has been measured in the red cells from twenty patients with hyperthyroidism. The mean concentration of sodium was 11·18 m-mole/l red cells; in sixty normal control subjects the mean red cell sodium level was 7·04 m-mole/l. The difference between these two groups was highly significant. There was no measurable difference between the potassium concentration and water content of red cells from thyrotoxic and control groups.
2. Measurements of active sodium efflux were carried out in red cells from ten hyperthyroid subjects and their matched controls. The rate constant for active sodium efflux was significantly lower in the patients than the control group.
3. The total amount of sodium actively pumped from red cells in 1 hr was significantly higher in the patients than the controls.
4. The total amount of sodium moving out of the red cells, both actively and by exchange diffusion, matched the total influx of sodium. This was true for control subjects and those with hyperthyroidism and this would support the view that the intracellular sodium concentration is constant and represents the result of a balance between influx and efflux. In hyperthyroidism this balance persists, but with an abnormally high intracellular sodium concentration.
5. There was a linear relationship between the cell sodium content and the active transport of sodium from the cell in control and hyperthyroid subjects.
6. Triiodothyronine did not produce any change in sodium transport by normal red cells in vitro.
7. It is concluded that there is a depression of the activity of the sodium pump in the red cells of hyperthyroid subjects. This allows the resting intracellular sodium concentration to rise until a new steady state is reached. Evidence is given that these changes are reversed when hyperthyroidism is corrected.