1. The activation curve of rubidium influx by external rubidium in rat red cells showed an inflexion at a concentration around 0.2 mM. This inflexion point was displaced to the right by ouabain.2. The removal of sodium from the external solution changed the characteristics of the activation curve of rubidium influx. At external rubidium below 0.5 mM the uptake increased whereas above that concentration there was marked reduction. Thus the sodium-free effect on rubidium uptake is dependent on the external rubidium concentration.3. With 0.25 mM rubidium, the relationship between increase of rubidium influx and reduction of external sodium followed a more or less exponential function. All the increment was ouabain-sensitive.4. With a rubidium concentration above 0.5 mM the reduction of the rubidium uptake, as sodium was removed, followed curves of complex shape. With 10 mM rubidium, when sodium was reduced from 5 mM to zero, there was an increase instead of a further reduction. These results suggest interactions of several effects.5. The ouabain sensitivity of the rubidium influx in rat red cells is smaller than in other systems studied up to now. The dose-response curve was shifted to the right as the rubidium concentration increased and a plateau was obtained with rubidium only below 1 mM at 10(-5)M ouabain. When plotted as a percentage of the maximal inhibition the points fell into the theoretical curve following a simple one reactant/one site reaction.6. Ouabain inhibition seems to be a complex function of at least three variables: the concentration of the glycoside, the concentration of sodium and the concentration of rubidium. When sodium was absent, 10 muM rubidium was able to prevent, to a great extent, the inhibition produced by 10(-5) and 10(-4)M ouabain.