We examined the hypothesis that reversal of hyponatremic hyperkalemic electrocardiographic changes through the infusion of saline solutions was due to the action of sodium ion in increasing the action potential rising velocity which is depressed when the cell is exposed to increasing concentrations of potassium. Using standard microelectrode techniques, the rising velocity of canine ventricular cells was shown to increase by 21%, whereas conduction time between two microelectrodes decreased 17% when the sodium concentration of the perfusate was increased from 120 to 163 mM in 2.7 mM potassium solution. When these cells were exposed to identical increases in sodium concentration in a 7.7-mM potassium solution, rising velocity increased 55% (P less than 0.005), whereas interelectrode conduction time decreased 33% (P less than 0.05). Similar changes were noted in experiments on human ventricular cells. These experimental findings are consistent with the hypothesis stated above.