The molecular basis for Na/Li exchange is unknown. Li can be transported by the Na pump, anion exchanger (AE1), a background leak and the Na/Li exchanger. In vivo the intraerythrocyte concentration of Li results from the balance of passive entry mostly on AE1 and the active extrusion on the Na/Li exchanger. In this paper we show that erythrocytes have Li-activated phosphate transport that behaves as if it is mediated by the Na-phosphate cotransporter (hBNP1) and provide evidence that this Na/Li-phosphate cotransporter is also the mechanism for Na/Li exchange. First, external lithium (> 20 mM) activated phosphate influx by several fold. Lithium activation of phosphate influx was potentiated by the presence of external sodium. Second, the ouabain-insensitive ²²Na efflux was stimulated by external lithium and then inhibited by external phosphate. Third, phloretin inhibited Na- and Li-activated phosphate flux with the same K_I, 0.25 mM. Fourth, external phosphate (0.1 - 1.0 mM) inhibited ouabain-insensitive lithium efflux only if external Na was present. Fifth, arsenate, a phosphate congener, inhibited both Na-PO₄ cotransport and Li-activated PO₄ flux with similar kinetics when Na or Li concentration was high, but did not inhibit Li_out/Na_in exchange when Li_out concentration was low. The collective results suggest that both Na and Li are substrates for at least two sites on the same phosphate cotransporter and that Na-Li exchange behaves as if it is mediated by this Na/Li-phosphate cotransporter when only one cation is bound. Plasma and intracellular phosphate concentrations may be important regulators of lithium transport and its therapeutic effects.