Nontoxic and toxic doses of digitalis glycoside produced a rapid release of potassium from the myocardium and from extracardiac tissues of the dog. For approximately 25 minutes after the administration of a digitalis glycoside the myocardium was in negative potassium balance and within an hour returned to positive balance. The most serious electrocardiographic changes transpired when the myocardium approached or attained potassium balance. Pretreatment with potassium chloride protected the heart against arrhythmias by increasing Ko+. Pretreatment with glucose and insulin enhanced the arrhythmic action of the digitalis glycosides presumably by producing a low serum potassium (Ko+) and possibly by modifying the state of intracellular potassium (Ki+).