Disobutamide suppresses ventricular arrhythmias in several in vivo animal models. In particular, disobutamide suppressed ventricular arrhythmias in ouabain-toxic dogs and in dogs in which myocardial infarction. Clear cytoplasmic vacuolation associated with disobutamide is an example of a remarkable morphologic change not associated with apparent overt toxicity based on various functional tests. Clinically in the dog if vacuolation was associated with cell injury, one might expect a chronic debilitating condition as seen in the case of many spontaneous genetic storage diseases. Chronic heart failure or a gastrointestinal motility disorder might occur as a result of the changes in the musculature of coronary arteries or gastrointestinal wall, respectively. Disobutamide, because of its apparent low toxicity, can be recommended as useful for investigations aimed at determining the borderline between physiologic limits and toxicity of intracellular drug storage and for advancing knowledge of mechanisms involved in xenobiotics entry and storage in cells. Disobutamide was withdrawn from clinical testing when clear cytoplasmic vacuoles were found in the rat and dog during toxicity studies. Disobutamide induced vacuoles in all cell types except rat leukaemia. The drug induced cell death and reduction in confluency or cell count in cultures of all cell types except rat carcinoma and rabbit aorta muscle.