The cardiomyopathic Syrian hamster develops focal myocardial necrosis beginning at 1 month of age, which leads to eventual ventricular failure within 1 year. The pathogenesis of this myocytolytic necrosis is unknown. Based on the nature of the cell necrosis, cytochemical evidence of vascular alterations, and the sensitivity of the hamsters to catecholamines and other vasoactive substances, we believe that the cardiomyopathy may be mediated by abnormalities of the microcirculation. Nonetheless, until the present study, no significant changes have been observed in these vessels. To elucidate the pathogenesis of this disease, we perfused living cardiomyopathic hamsters with silicone rubber solutions, which revealed numerous areas of microvascular constriction, diffuse vessel narrowing and luminal irregularity. Fixed structural lesions in these vessels could not be demonstrated. Pretreatment of young hamsters with verapamil during the period when they normally develop myocardial necrosis prevented myocytolytic lesions and abolished microvascular hyperreactivity. We believe that focal, transient spasm of small blood vessels, probably secondary to vasoactive substances, may cause myocytolytic necrosis (a form of reperfusion injury) in this model. This may also be a multifactorial disease with myocellular as well as vascular abnormalities leading to myocardial degeneration. The similarity of this disease to human and experimental cardiomyopathy suggests that microvascular spasm may be a common denominator of many different cardiomyopathic syndromes.