In an attempt to characterize the role of p53 alterations in the pathogenesis of intracranial neuroectodermal tumors, 196 tumors were immunostained with a monoclonal antibody against the p53 protein on archival materials of formalin-fixed, paraffin-embedded materials. Only 11% of well differentiated astrocytomas stained positive, whereas up to 40% of high-grade astrocytomas (anaplastic astrocytomas and glioblastoma multiforme) were immunolabelled. The extent of immunolabelling of tumor cells also increased from the low-grade to high-grade astroctyomas. Among the high-grade astrocytomas, the small anaplastic cells were the predominant cell type which exhibited aberrant p53 protein accumulation. Rare cases of oligodendrogliomas and medulloblastomas also stained positive, whereas ependymomas and choroid plexus tumors were uniformly negative. p53 alterations therefore appear to play a role in the progression from low-grade to high-grade astrocytomas and the cell type which appeared to be critically involved appeared to be the small anaplastic cells.