This paper describes the effects of a number of cardiac glycosides on the movements of sodium and potassium across the human red cell membrane. A preliminary account of some of the experiments reported here has already been published (Glynn, 1955). The aim of the work was, first, to decide whether the glycosides acted directly on the transport mechanism, and, secondly, to see if the effects of the glycosides could be made to yield any information about the molecular basis of cation transport.Many substances affect the movements of sodium and potassium but practically all of them act indirectly. Some, like the lysins, make the membrane leaky and so increase 'downhill' fluxes; others, like iodoacetate, inhibit energy metabolism and prevent active transport. In 1953 Schatzmann found that strophanthin, an active principle from Strophanthus gratus, prevented the uptake of potassium and elimination of sodium that normally occur when cold-stored red cells are incubated with glucose at 370C. Other cardiac glycosides have been found to give similar results (Joyce & Weatherall, 1955;Kahn & Acheson, 1955). Schatzmann, in his original paper, noted that concentrations of glycosides sufficient to affect ion movements had no effect on oxygen consumption or on lactic acid formation, and he concluded that the action of the drugs lay beyond the stage of energy production. It follows that the glycosides must act either by preventing energy released during glycolysis from reaching the ionic pump, or by interfering with the carrier mechanism itself. These two theories lead to different predictions, and experiments will be described which show that it is probably the second that is correct. The cardiac glycosides thus emerge as the only substances-apart of course from the metallic cations-which there is, at present, reason to believe act on the carrier system.It is of interest to know how much of the structure of the glycoside molecule is necessary for the action on the ion fluxes, and an attempt has been made

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