A rise in intracellular sodium during periods of exposure to calcium free media would seem to be the critical step that predisposes the mammalian heart to the damaging effects of the calcium paradox. The damage which is seen in both single cells and multicellular preparations, occurs on reperfusion with calcium containing media and results from calcium loading via the sodium/calcium exchanger where the rise in intracellular calcium provokes hypercontraction as well as activating hydrolytic enzymes. Because the rise in intracellular sodium is a critical step in inducing damage, manoeuvres which reduce this rise during calcium depletion are expected to protect the heart against the calcium paradox. Raising extracellular magnesium concentration is one such manoeuvre which by blocking the influx of sodium through the L-type calcium channels, reduces the rise in intracellular sodium during calcium depletion. The beta-amino acid taurine is another agent capable of opposing a rise in intracellular sodium. Taurine is present at high concentration in mammalian heart cells and is maintained against high concentration gradient. During calcium depletion, heart cells use this energy to efflux taurine and sodium via a taurine/sodium symport and therefore protect against the calcium paradox. A similar mechanism may also be used by the ischaemic heart to reduce the rise in intracellular sodium. In contrast to the changes seen during the calcium paradox the ischaemic heart shows a rise in intracellular magnesium concentration. This rise will have several and diverse cellular effects including the modulation of intracellular calcium mobilisation and of several membrane transporters. The potential significance of these effects remains to be evaluated. On the other hand elevated levels of extracellular magnesium may protect the ischaemic heart by reducing the influx of calcium by suppressing the L-type calcium channels and possibly the sodium/calcium exchanger. Finally evidence suggests that the rat heart may not be identical to that of other species in its response to the calcium paradox and to the protective role of intracellular taurine and extracellular magnesium. The reason for this species difference would seem to be due to different metabolic activity and the activity of the sodium, potassium-ATPase.