Hypereosinophilia is associated with clonal disorders, reactive conditions, and rarely with idiopathic hypereosinophilic syndrome (IHES). We investigated whether measurement of eosinophilic activity using the plasma eosinophil cationic protein (ECP) level, interleukin-5 (IL-5) level, and the ratio of eosinophilic cationic protein/eosinophil count (ECP/Eo) could improve the early differentiation among various eosinophilic diseases: IHES (n = 9), clonal disorder (n = 35), reactive eosinophilia with malignancy (n = 30), and reactive eosinophilia with inflammation (n = 46). The 120 eosinophilic patients had higher plasma ECP and IL-5 levels than the non-eosinophilic control group (p <0.05). The 9 patients with IHES had significantly higher plasma ECP and IL-5 levels than patients with other eosinophilic diseases (p <0.05). The plasma levels of ECP and the ECP/Eo ratio were higher in patients with non-haematologic malignancy than in those with other reactive eosinophilias (p <0.05). This study shows that levels of plasma ECP, IL-5, and ECP/Eo ratio may assist in the clinical differentiation of various eosinophilic diseases.