Myocardial ischemia was produced in six dogs by arterial occlusion. Tissue contents of H2O, Na, Ca, and amino acids increased; K and (in one dog) Mg decreased. Variability in composition increased. Cell changes were evaluated with a method of appraising variability in composition between biopsies, and calculated (in three dogs) using extracellular fluid (ECF) volumes measured with [60Co]EDTA. Cell contents of H2O, Na, Cl, Ca, amino acids, and the molar quantity of nondiffusible solutes increased. Contents of K, nondiffusible anions (epicardium only) and total ionic strength of cell fluid decreased. Clinical implications are discussed.