Immunohistochemical study of erythropoietin in cerebellar hemangioblastomas associated with secondary polycythemia. Although cerebellar hemangioblastomas are known to be associated with secondary polycythemia, the cellular derivation of erythropoietin (EPO) in hemangioblastomas still remains obscure. Specimens from 18 patients with cerebellar hemangioblastomas were immunohistochemically studied using anti-EPO monoclonal antibody. Eight cases of brain tumors, including 2 meningiomas, 2 medulloblastomas, 2 glioblastomas, and 2 metastatic brain tumors were studied as controls. In 9 of 18 cases, EPO-positive cells were scattered around the capillaries and were ultrastructurally shown to be mast cells. These cases were not, however, associated with secondary polycythemia. In contrast, the stromal cells were positive for EPO in 3 cases. Among them, one was associated with secondary polycythemia. Furthermore, one-half of the control cases of brain tumor contained EPO-positive mast cells. Accordingly, it was suggested that mast cells (or small granulocytes) have little relationship to the release of EPO; however, some stromal cells might release EPO with a resultant polycythemia. 