1. Present results confirm our previous work which showed that a sodium intake over 3 mmol day−1 kg−1 decreased the total erythrocyte efflux rate constant in untreated males with essential hypertension.
2. The infusion of saline (2.25 mmol of Na+/kg) over 30 min decreased the efflux rate constant.
3. The change after chronic sodium loading and the intravenous infusion of saline is in the ouabain-sensitive component (ouabain-sensitive Na+, K+ ATPase pump activity) of total efflux.
4. The reduction in efflux by an acute sodium load occurred only when chronic sodium intake was low.
5. Posture did not affect the efflux rate constant whether sodium intake was high or low.
6. The reduction in efflux after chronic ingestion and acute administration of sodium occurred only when erythrocytes were incubated in plasma. It did not occur in artificial medium, which suggested that a plasma factor mediated the effect of added sodium on cell sodium efflux.
7. The effect of sodium on cell sodium transport by a plasma factor with ouabain-like properties (which may be a natriuretic hormone) constitutes a regulatory system. This system, the sodium-ouabain-vsensitive cell sodium-transport pathway system, has important implications for the understanding of blood pressure control and sodium homeostasis.