An electrocardiographic (ECG) and histological study was performed to compare the prevention of digoxin toxicity in rabbit heart by active immunisation and long term prophylactic treatment with the antiarrhythmic mexiletine. Both specific digoxin antibodies and mexiletine prevented the induction of electrophysiological effects of digoxin, while active immunisation was more effective than mexiletine in preventing histological damage to the myocardium. Severe ECG and histological alterations have been observed in animals with no prophylactic treatment. Therefore, we assume that active immunisation may be more effective than long term prophylaxis with mexiletine in preventing the toxicity of digoxin; the possible clinical usefulness of both methods is discussed.