Triple quantum (TQ)-filtered 23Na NMR spectroscopy and the shift reagent, TmDOTP5-, have been used to evaluate the contributions of intra- (Na+i) and extracellular (Na+e) sodium to the TQ-filtered signal in the rat liver, in situ. Na+e contributed significantly to the total TQ-filtered signal in live animals, and the intensity of this signal did not change postmortem. The TQ-filtered Na+i signal increased by approximately 380% over a period of 1 h postmortem, whereas the single quantum (SQ) Na+i increased by 90%. The constancy of the TQ-filtered Na+i signal indicates that changes in total TQ-filtered 23Na signal intensity in liver (without a shift reagent) may accurately reflect changes in TQ-filtered Na+i signal intensity. The large percent increase in the TQ-filtered Na+i signal as compared to the SQ signal suggests that the fraction of Na+i interacting with macromolecules increases after death.