The specific binding of digitalis glycosides to the Na,K-ATPase is used as a tool for Na,K-ATPase quantification with high accuracy and precision. In myocardial biopsies from patients with heart failure, total Na,K-ATPase concentration is decreased, and the decrease in Na,K-ATPase concentration correlates with a decrease in heart function. During digitalization, a fraction of remaining pumps are occupied by digoxin. No evidence for an endogenous digitalis-like factor of any clinical importance was obtained. It is recommended that digoxin be administered to heart failure patients who still have dyspnea after institution of mortality-reducing therapy.