Amiloride-inhibitable Li⁺ influx in dog red blood cells is mediated by the Na⁺/H⁺ exchanger, NHE. However, there are substantial differences between the properties of Li⁺ transport and Na⁺ transport through NHE. Li⁺ influx is activated by cell shrinkage, and we reported earlier that Na⁺ influx is not (Dunham et al. Am J Physiol Cell Physiol 287: C336-C344, 2004). Li⁺ influx is a sigmoidal function of its concentration and Na⁺ activation is linear at low Na⁺ concentrations. Li⁺ does not inhibit is own influx; in contrast Na⁺ inhibits Na⁺ influx. Li⁺ prevents this inhibition by Na⁺. Na⁺ is a mixed or noncompetitive inhibitor of Li⁺ influx, implying that both a Na⁺ and a Li⁺ can be bound at the same time. In contrast Li⁺ is a competitive inhibitor of Na⁺ influx, suggesting Li⁺ binding at one class of sites on the transporter. Since the properties of Li⁺ transport and Na⁺ transport are different, a simple explanation is that Na⁺ and Li⁺ are transported by separate sites. The similarities of the properties of Li⁺ transport and the inhibition of Na⁺ transport by Na⁺ suggest that Li⁺ is transported by the Na⁺ inhibitory sites.