In this issue of Blood, Doyle et al provide evidence that knockout of the genes encoding the two most abundant eosinophil secondary granule proteins disrupts the normal differentiation of eosinophils from progenitors in the bone marrow, providing a novel strain of mice with a highly specific deficiency in eosinophilopoiesis and, therefore, eosinophils. This strain is likely to be used by investigators to elaborate the normal vs pathogenic roles of eosinophils in health and disease.