Magnesium plays an important role in a large number of cellular processes by acting as a cofactor in enzymatic reactions and transmembrane ion movements. Magnesium is a modulator of Na,K ion transport systems in numerous tissues. In this study, the interactions between magnesium and Na,K pathways are described. In the paracellular pathway, Na,K transports are generally increased by Mgo. In the cellular pathway, there are various processes: (1) Potassium channels-Mgi blocks the outward currents, first by interfering with the passage of K+ ions and inducing rectification of the channel current-voltage relationship, and secondly by completely blocking the channel pore and reducing the channel open probability: Mgo increases the K+ channel permeability in a leaky membrane. (2) Sodium channels-Mgi blocks outward currents in a voltage- and dose-dependent manner, acts as a fast blocker by screening of surface charges, and produces an open channel block in several Na+ channels; Mgo increases Na+ transport in toad bladder and human amnion at high concentration by acting on the driving force of the sodium pump. (3) Na/K pump-Mgi and Mgo stimulate the Na/K exchange at low concentration and inhibit it at high concentration, by a stabilization of E2 forms of the enzyme which would reduce the rate of turnover of the pump. (4) Na-K-2Cl cotransport increasing Mgo concentration stimulates this system in red cells and human amnion, and the bumetadine-sensitive K+ transport is sensitive to Mgi (5) Kcl cotransport-The increase in Mgi inhibits this cotransport. (6) Na-H antiport-Na/H exchange responds to manipulations of cell magnesium but the effect is probably not a direct one; magnesium is required not for the transport process per se, but for the transduction of the volume stimulus (7) H-K pump Mg activates this system. (8) Na-Ca antiport-The activity of this antiporter is inhibited by Mgo; the inhibition by magnesium is competitive with calcium. (9) Na-Mg exchange-in this system, the Na+ gradient provides the energy for net Mg2+ extrusion. In conclusion, intracellular and extracellular magnesium may be an important physiological regulator of the sodium and potassium pathways in the cell.