Vacuolation of oligodendroglia, a new type of cytopathological change, has been described. The change is observed frequently at the perifocally edematous cerebral white matter adjacent to the metastatic lesions of carcinoma from the lung in all three cases examined. It is also present occasionally in association with astrocytoma. This condition is characterized by swelling of oligodendroglias due to numerous cytoplasmic vacuolations which contain the material identical with that of the extracellular edema fluid. In such cells, the nucleus is displaced and deformed by vacuoles but the nuclear chromatin and envelopes are arranged normally. By occupation of numerous large vacuoles the cytoplasm is divided into small areas, but the individual organelles are only minimally altered. The oligodendroglial vacuolation seems to be a phagocytic response to the edema fluid which contains proteinous macromolecules derived from blood-borne protein and necrotic material of brain tissue and neoplastic cells. The vacuolation may result in some oligodendroglial dysfunction in maintenance of myelin and probably be related with diffuse loss of myelin sheath in the longstanding brain edema secondary to neoplastic invasion. The vacuolated cells can be identified with light and electron microscopes in Epon-embedded sections of surgically removed tissue but not in paraffin sections.