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1. The effect of amiloride on the influx and efflux of ²⁴Na and ⁴²K in red cells was studied. The drug was added to the bathing Ringer or else incorporated in resealed ghosts.

2. Amiloride does not inhibit the active or the passive (ouabain insensitive) extrusion of ²⁴Na.

3. Amiloride inhibits the influx of ²⁴Na into red cells by 70%.

4. Whether added to the inside or to the outside of the cells amiloride has no effect on the efflux of ⁴²K.

5. Amiloride does not modify the uptake of ⁴²K from control Ringer. This uptake is strongly inhibited by the removal of Na. Amiloride has no effect on the extent of this inhibition.

6. It is concluded that amiloride specifically inhibits the passive penetration of Na, and has no effect on the Na-K-pumping mechanism. However, at the concentration which inhibits 70% of the influx, amiloride fails to produce an observable effect on the ouabain-insensitive Na-efflux.

7. On the basis that the information obtained could be extrapolated to other membranes, the effect of amiloride on epithelial membranes is discussed.