$\sp7$Li NMR spectroscopy has been used to investigate the transsarcolemmal transport mechanisms responsible for the increase in intracellular sodium that occurs during global ischemia in the isolated rat heart. Hearts were perfused with a modified Krebs Henseleit buffer containing 78 mM sodium and 78 mM lithium, lithium being a biological congener for sodium with twice the sodium NMR sensitivity. The NMR relaxation times for lithium were investigated in the perfused heart and buffer solutions. The addition of the shift reagent, DyTTHA$\sp{3-}$, shortened the relaxation times for lithium in buffer and enabled the discrimination of intra- and extracellular lithium. Lithium moved into the myocardial cells with a rate constant (k$\sb{-1}$) of 0.068 min$\sp{-1}$, a t$\sb{1/2}$ of 10.3 min and an initial rate of increase of 5.27 mM/min, while lithium noved out of the heart with a k$\sb{-1}$ of 0.062 min$\sp{-1}$, a t$\sb{1/2}$ of 11.2 min and an initial rate of 4.83 mM/min. Lithium equilibrated in the heart with equal concentrations on either side of the sarcolemma, not in equilibrium with its electrochemical gradient. Perfusion with the low-sodium, lithium-containing buffer had a positive inotropic effect on the heart with no effect on the steady state levels of the myocardial high energy phosphates. The myocardial rate pressure product increased by 114% while the ATP and PCr concentrations, measured using $\sp{31}$P NMR spectroscopy, varied by less than 8%. ICP-AES analysis of hearts showed that as lithium accumulated in the cells, it displaced both sodium and potassium. Finally, intracellular lithium increased during myocardial ischemia with a linear rate of 1.34 mM/min, similar to the rate of increase of intracellular sodium during ischemia. This increase was completely blocked by the Na$\sp+$/ H$\sp+$ exchange inhibitor, amiloride. (Abstract shortened by UMI.)