Since previous published studies of astrocytomas have shown alterations in the short arm of chromosome 17, and this chromosomal location is that which encodes the p53 protein, we used a monoclonal antibody and immunocytochemistry to detect this protein in a series of brain biopsies. The normal p53 protein has a short half-life and is not detectable using this method. Expression of an altered p53 protein was detected in 29 of 71 brain biopsies, but only in those that showed astrocytic features. p53 expression was detected in 20/32 glioblastomas, 5/12 anaplastic astrocytomas, and 3/5 mixed anaplastic oligo-astrocytomas, but only in astrocytic cells. It could not be detected in any other histologic types of primary brain neoplasms, either benign or malignant. The protein was detected in only 1/11 biopsies interpreted as showing gliosis, but this was in a patient who had previously had a resection for glioblastoma, and may have represented unrecognized infiltrating astrocytoma cells. The p53 protein was also expressed in the nuclei of the two human astrocytoma cell lines examined, U251MG and D54MG. These results are in general agreement with previous detailed chromosomal analyses that have found loss of heterozygosity in up to 60% of malignant astrocytic gliomas.