A combination of 31P and 23Na NMR spectroscopy has been used to quantify the concentration of intracellular sodium, [Na]IC in the isolated and perfused mouse liver. The 31P resonances of dimethyl methylphosphonate and LaDOTP5-, markers of total tissue space and extracellular space, respectively, were used to determine the intracellular liver volume. For a mean wet weight of 1.7 +/- 0.3 g, the intracellular liver volume as measured by 31P NMR averaged 1.2 +/- 0.2 ml. The amount of intracellular sodium was measured from the baseline-resolved intracellular 23Na resonance during perfusion of the shift reagent, TmDOTP5-. These two measurements resulted in an NMR-determined value for [Na]IC of 29.0 +/- 5.2 mM. Separate measurement of total tissue Tm and Na by atomic absorption spectroscopy on the same samples provided an AAS-determined value for [Na]IC of 32.1 +/- 7.4 mM. These results indicate that intracellular sodium in the isolated, perfused liver is 100% visible by 23Na NMR spectroscopy.