The Na+, K(+)-activated adenosine triphosphatase (ATPase) is present in the membrane of eukaryotic cells and represent a major pathway for Na+ and K+ transport across the plasma membrane. Cardiac glycosides, such as digoxin or ouabain, inhibit this enzyme activity by binding to a specific receptor on the membrane. Studies conducted in this and other laboratories have proven the existence of digitalis-like compounds in animal and human tissues which may serve as regulators, in vivo, of the Na+, K(+)-pump activity. The levels of digitalis-like compounds in the plasma are increased in hypertension and other illnesses. A possible link at the cellular and molecular level between these compounds and etiology of arrhythmias, an important cause of morbidity and mortality in patients with various diseases of the heart, can be postulated: Na+, K(+)-ATPase activity contributes directly and indirectly to the electrical membrane potential of cardiac cells. The inhibition of this pump by the endogenous digitalis-like compounds, in discrete areas of the heart, can induce changes of the membrane potential of these cells. These changes may cause an increase in excitability of the particular cells and contribute to the generation of arrhythmias.