The Syrian cardiomyopathic hamster has a hereditary disease in which a progressive myocardial necrosis mimics human forms of cardiac hypertrophy. Lesions are associated with calcium overload and can be prevented with the calcium antagonist verapamil. Numbers of receptor binding sites for calcium antagonists in heart, brain, skeletal muscle, and smooth muscle were markedly increased in cardiomyopathic hamsters. The uptake of calcium-45 into brain synaptosomes was also increased in cardiomyopathic hamsters. The increase in calcium antagonist receptors and related voltage-sensitive calcium channels may be involved in the pathogenesis of this cardiomyopathy.