Apolipoprotein E is expressed in neurofibrosarcoma and Schwannoma cell cultures derived from two patients with different types of neurofibromatosis, but not in six cell cultures derived from the benign neurofibromatosis neurofibromas. In addition, a cell culture derived from a nonneurofibromatosis human malignant astrocytoma showed apolipoprotein E expression. Although all cells in either the neurofibrosarcoma or Schwannoma cultures appeared morphologically similar (suggesting homogeneity), apolipoprotein E was immunochemically detected in the perinuclear region of only half of the cells. Thus, production of apolipoprotein E in neurofibromatosis-associated neurofibroma tumors may be a marker for a specific subclass of transformed cells. The expression of apolipoprotein E in glial cell neoplasms is possibly related to an alteration in their lipid metabolism.