Epidemiological studies indicate a strong relationship between dietary Mg intake and the incidence of sudden cardiac death. The mechanism by which dietary Mg leads to an increased incidence of cardiovascular disease is unknown but may involve alteration of electrolyte balance. In the present study, tissue electrolyte levels and myocardial pathology were investigated in adult hamsters fed a diet containing no added Mg. Control animals were fed the same diet supplemented with Mg or standard laboratory chow. Hamsters were killed after 4, 8, 12, or 18 days on the test diet, and levels of Na, K, Ca, and Mg were measured in the serum, myocardium, bone, and kidney. The earliest change induced by the test diet was a decrease of the serum Mg and an increase in the Na concentration of the myocardium and other tissues. Following the rise in myocardial Na, the myocardial Ca rose, attaining a fourfold increase by 18 days. K fell in heart and kidney, but not significantly. Although there was no significant change in myocardial Mg, foci of myocardial necrosis, considered to be typical of acute severe Mg deficiency, were found. Myocardial necrosis and the increase in myocardial Ca occurred in parallel. Because of the pattern of observed changes in electrolyte levels, and the potential role of Ca in myocardial injury, the occurrence of myocardial necrosis in these Mg-deficient hamsters is attributable to the increased level of myocardial Ca, rather than to any change in intracellular Mg levels. It is postulated that reduced extracellular Mg levels increase [Na]i through reduction of sarcolemmal (Na+ + K+)-ATPase activity. This would lead to an increase in [Ca]i through Na-Ca exchange.