The rate constant of the Na+ efflux of human erythrocytes in isotonic solutions of various ionic strength varied over NaCl concentration was measured. The Na+ efflux remained constant over a wide range of ionic strength. Only under conditions where the transmembrane potential was near O mV, a local minimum could be detected. The rate constant of the ouabain-insensitive part of the Na+ efflux exhibited a strong increase at reduced exterior ionic strength. When reducing the extracellular NaCl concentration and at the same time equivalently increasing the extracellular KCl concentration in solutions of physiological ionic strength, a reduction of the rate constant of the Na+ efflux was found. It was established that an increase of the intracellular pH increases the rate constant of the Na+ efflux. A change of transmembrane potential from -7 to 52 mV at constant intracellular pH had no influence on the Na+ efflux. The change of the exterior surface potential of erythrocytes by preincubation with neuraminidase had no influence on the Na+ efflux in the range of the ionic strength studied.