The action of adenosine on atrial functional refractory period, as well as on its ability to interrupt atrial flutter is similar to that of digitalis. The latter suggests the possible existence of an adenilic component to digitalis action. To test this possibility, we measured the plasma concentrations of adenosine after ouabain infusion in dogs, and we investigated the effect of digitalis on atrial refractory period and on flutter in conditions of cholinergic inhibition and purinergic blockade. Ouabain was administered until ventricular fibrillation was induced. Blood was obtained from both the coronary sinus and the femoral vein, and adenosine was measured by liquid chromatography. The refractory period was measured by applying an extra stimulus at variable intervals following a train of 10 basic beats. Flutter was induced by stimulation of the posterior internodal pathway. RESULTS The concentration of adenosine in plasma collected from the coronary sinus increased by more than 100%; the effect of digitalis on atrial refractory period was independent of cholinergic blockade, but it was inhibited by aminophylline; the ability of digitalis to interrupt flutter was modified by aminophylline. CONCLUSIONS The antiarrhythmic action of digitalis seems to include an adenilic component, that results from the liberation of adenosine in the heart.