Manganese superoxide dismutase (MnSOD) is a superoxide anion scavenger located in mitochondria. Increased expression of MnSOD can diminish oxygen radical-mediated injuries and the cytotoxic effects of tumor necrosis factor alpha, ionizing radiation, and certain chemotherapeutic agents. We used immunohistochemical staining to analyze 42 specimens of human brain tumors and 3 normal brain controls with a polyclonal antibody recognizing human MnSOD. We measured MnSOD in cerebrospinal fluid (CSF) from 14 patients with brain tumors and 7 control patients using an ELISA. Although MnSOD is not readily detected in normal brain, malignant central nervous system tumors, including tumors metastatic to the brain, displayed marked immunoreactivity to MnSOD intracellularly, in the extracellular matrix and in the tumor endothelial cells. Grade IV astrocytomas (glioblastomas), Grade III astrocytomas, and medulloblastomas were strongly immunoreactive, whereas Grade II astrocytomas had much less immunoreactivity. ELISA analysis of CSF samples from patients with malignant tumors also revealed high levels of MnSOD protein, up to 45-fold greater than the level of control CSF samples.