The hypereosinophilic syndrome (HES) is a rare yet frequently fatal disorder of unknown etiology characterized by markedly elevated eosinophil counts and subsequent multiple organ failure due presumably to eosinophil-derived protein toxicity. We describe the laboratory and anatomic findings in a 15-year-old female with extraordinarily high circulating levels of eosinophil major basic protein (MBP) who sustained a precipitous cardiac death secondary to a massive myocardial infarction. Postmortem examination showed marked cardiomegaly with extensive recent left ventricular infarction. Occlusive thrombosis of small blood vessels was evident in the myocardium, spleen, lungs, and kidneys. Immunofluorescent staining showed massive MBP deposition in multiple organ parenchyma including the heart, renal glomeruli, adrenal cortex, bronchioles, and other visceral organs, suggesting a causal relationship. We hypothesize on the mechanisms of eosinophil toxicity in HES.