1. A study has been made of the dependence on the concentrations of internal Na(+) and external K(+) of lactate and phosphate production in human erythrocytes. 2. Lactate production was stimulated by Na(+) and K(+) but only when they were internal and external respectively. The stimulation was counteracted by ouabain. The production of phosphate was affected in the same way. 3. There is a quantitative correlation between these effects and those previously found for cation movements and the membrane adenosine triphosphatase. 4. It is concluded that the rate of energy production in glycolysis is partly controlled by the magnitude of active transport; the extent of this regulation is shown to vary from 25 to 75% of a basal rate that is independent of active transport. 5. The activity of the membrane adenosine triphosphatase was also compared with rates of Na(+) and K(+) transport. The latter were varied by altering the concentrations of internal Na(+) and external K(+), and by inhibiting with ouabain. 6. A threefold variation of active transport rate was accompanied by a parallel change in the membrane adenosine-triphosphatase activity. The results show a constant stoicheiometry for the number of ions moved/mol. of ATP hydrolysed, independent of the electrochemical gradient against which the ions were moved. 7. Calculations show that the amount of ATP hydrolysed would provide enough energy for the osmotic work. The results are discussed in relation to possible mechanisms for active transport.

Directional effects of ions on a chemical mechanism are implied by the complex way in which active transport processes depend on the ionic composition of the fluids bathing the cell membranes. There appears to be an interdependence of cation movements, for an ion is transported in one direction only when another ion is moved in the opposite direction. The net extrusion of Na+ ions from erythrocytes requires the presence in the medium of K+ ions, which are simultaneously taken up (Harris & Maizels, 1951; Glynn, 1956; Post & Jolly, 1957). It is this coupled movement of Na+ and K+ ions that is inhibited by cardiac glycosides, probably from the external surface of the cell (Glynn, 1957). Other ions, notably Rb+, NH4+, Cs+ and Li+, may replace K+ ions both in being accumulated and in facilitating Na+ ion efflux (

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