The production of amyloid beta protein precursor (APP), which is a potent inhibitor of matrix metalloproteinases and serine proteinases, in human astrocytic tumors (n = 17) and normal brain tissues (n = 3) was investigated. We found proteinase inhibitory activity at around 120 kD by trypsin reverse zymography in the culture media of explant cultures of anaplastic astrocytomas and glioblastomas, but not in those of astrocytomas and normal brain tissues. Immunohistochemistry using a monoclonal antibody against human APP demonstrated that APP was detectable mainly in tumor and endothelial cells. Semiquantative analysis of western blotting revealed that immunoreactivity for APP in the culture media of tumor explant cultures appeared to be increased associated with the malignancy of astrocytic tumors. These findings suggest that APP production may be related to the malignant progression of human astrocytic tumors.