We examined the effect of low Na concentrations (25 mM) in Ca-free solutions on the myocardial damage induced by the Ca paradox in guinea pigs using electron microscopy and electrophysiological methods. Ultrastructural damage consist of contraction bands, swelling of mitochondria and disappearance of major part of contractile apparatus induced by the Ca paradox was prevented by reducing Na from 145 to 25 mM in the Ca-free solution. The penetration of lanthanum into the myocardial cells, which was induced by the Ca paradox, was also prevented by reducing Na concentration during the Ca depletion period. Perfusion with Ca-free solution containing normal Na (145 mM) for 10 min caused a significant prolongation in the action potential duration (APD) of left ventricular papillary muscle, and reperfusion with Ca containing solution caused depolarization. The perfusion with Ca-free solution containing low Na concentration (25 mM) significantly reduced APD, but APD returned almost to control values without depolarization after reperfusion with Ca-containing solution for 5 min. These results suggest that the Na concentration in a Ca-free solution plays an important role in the pathogenesis of the Ca paradox phenomenon in guinea pig hearts.