Beagle puppies were chronically depleted of potassium, magnesium or of both cations simultaneously by dietary means. After eight weeks on deficient diets these animals and a control group were digitalized with acetylstrophanthidin. Potassium-deficient animals and animals deficient in both potassium and magnesium required 60 per cent of the control dose of acetylstrophanthidin to produce toxicity. The ensuing arrhythmias were of prolonged duration. Heart block of advanced degree, ventricular fibrillation and cardiac standstill occurred only in puppies deficient in potassium and in potassium and magnesium. Magnesium deficient animals showed prolonged digitalis toxicity but required normal doses of drug to produce ventricular tachycardia. Death following digitalization occurred in all deficient groups. Digitalization resulted in a rise in serum potasium which was most marked in magnesium-deficient and control animals. T wave peaking occurred during digitalization and was related to the increase in arterial potassium concentration. Control animals showed a reduction in serum magnesium during digitalization.