This is the first report that suggests that azelastine hydrochloride (AZE) and biscoclaurine alkaloids (CEPH; Cepharanthin®; Kaken Shoyaku, Tokyo, Japan) are useful in the treatment of idiopathic hypereosinophilic syndrome (HES). A 9-year-old boy was referred to our hospital because of fever and a cutaneous eruption. Full blood examination showed a normal hemoglobin level and leukocytosis of 66 400 /µL with 95% mature eosinophils. There was no history of allergy, no clinical or serological evidence of a parasitic infection and no evidence of a connective tissue disease, neoplastic disease, leukemia or immunodeficiency. The patient was treated with prednisolone, which induced a rapid but not sustained remission. Cepharanthin was then given to reduce the dose of the intermittent courses of prednisolone required. Azelastine HCl, prescribed by an otolaryngologist for perennial rhinitis when the patient was also receiving CEPH, unexpectedly reduced and maintained the eosinophil count at normal levels. Ultimately, AZE alone was tried and was ceased after 3.5 months; however, 5 weeks after discontinuation of AZE therapy, the eosinophil count had risen again to >25 000 /µL. After reinstitution of AZE with CEPH followed by AZE alone, the patient did well for 30 months, so the AZE was ceased. Eleven months later the eosinophil count again increased. Reinstitution of AZE with CEPH in doses proportional to the weight increase that had occurred in the interim resulted in a complete resolution of symtoms. Azelastine HCl with or without CEPH may be effective in HES patients, enabling the adverse effects of long-lasting steroid therapy to be minimized.