In isolated epithelia of rabbit descending colon the short-circuit current (Isc) is solely attributable to net transepithelial Na-transport, which in turn is identical with the unidirectional Na-influx across the luminal cell membranes. Amiloride blocks Isc by inhibiting luminal Na-influx into the cells. The type of inhibition exerted by amiloride in this tissue has to be termed mixed-type, since both the affinity of Na to its transport system and the maximal transport capacity are reduced. Na, on the other hand, is a competitive antagonist of the amiloride effect with a Ki of 136 mM; therefore KA, the amiloride-concentration at which the amiloride-effect is half-maximal, is increased from 0.14 microM at 5 mM Na in the incubation medium to 0.29 microM at 140 mM Na. It is conceivable that an "amiloride-like" action of Na may be responsible for the saturability of luminal Na-influx with increasing Na-concentrations.