. Salt sensing in animals involves the epithelial sodium channel (ENaC). If ENaC were involved in human salt sensing, then the lingual surface potential (LSP) would hyperpolarize when exposed to sodium. We developed a chamber to measure the LSP while different solutions superfused the surface of the tongue and a technique to adjust for the junction potentials induced by varying salt concentrations. Changing the superfusion solution from rinse solution (30 mM KCl) to 300 mM NaCl (ϩ30 mM KCl) caused the LSP to hyperpolarize by 10.1 Ϯ 0.7 mV (n ϭ 13, P Ͻ 0.001). With repeated challenge the LSP response was reproducible. Increasing the Na concentration from 100 to 600 mM increased hyperpolarization by 35 Ϯ 4.8% (n ϭ 9, P Ͻ 0.001). To examine whether amiloride affects the LSP, 0.1 mM amiloride was added to 300 mM NaCl; it reduced the hyperpolarization by 18.5 Ϯ 4.3% (P Ͻ 0.005, n ϭ 11). However, the amiloride effect was not uniform: in six volunteers, amiloride inhibited the LSP by as much as 42%, while in five subjects, amiloride inhibited Ͻ5% of the LSP. In an amiloride sensitive volunteer, amiloride exerted 50% of its effect at 1 M. In conclusion, we have demonstrated that the LSP can be measured in humans, that Na hyperpolarizes the LSP, that increasing the Na concentration increases LSP hyperpolarization, and that amiloride inhibits the Na evoked LSP in some humans. While ENaC is involved in sensing salt, its role appears to vary among individuals.