The principal effect of cardioactive glycosides (CG) is the inhibition of the (Na+ + K+)-ATPase system with subsequent increase in contractility of the myocardium. In subtoxic and toxic concentrations, CG increase O2 consumption due to a transient Ca2+ overload. Furthermore, the activity of several enzymes of the citrate cycle is changed; cAMP transiently rises with reduction of myocardial ATP, and intracellular lactate dehydrogenase and creatine kinase are lost in the coronary fluid. The antagonistic action of beta-receptor blocking agents is caused by their membrane-stabilizing effect. O2-consumption is increased in the non-failing heart, while in the failing one it decreased. The CG-induced arrhythmias are caused (1) by inhibition of the ATPase system of excitable cardiac structures, and (2) by interaction of CG with the autonomic nervous system. Severe intoxications and the rapid disappearance of cardiac symptoms upon administration of Fab fragments suggest that the CG-induced changes on the molecular level (with the exception of those on the ATPase system) are of secondary significance.