Fluorine-19 nuclear magnetic resonance (NMR) studies of cells and perfused organs loaded with fluorinated ion chelators represent a new approach to determining cytosolic free calcium levels in situ. The molecular basis for this approach and the relative advantages and disadvantages of the NMR technique are discussed in this paper. Results obtained on perfused normoxic and ischemic rat hearts are presented, indicating that ischemia is associated with an elevation in the level of cytosolic free calcium before the onset of irreversible cell injury. The results are therefore consistent with this elevation playing a causative role in the mediation of myocardial cell injury resulting from ischemia.