The presence and localization of bikunin (HI-30, or acid-stable protease inhibitor), a light chain of inter-alpha-trypsin inhibitor, was examined in 30 brain tumors employing immunohistochemical methods. The brain tumors involved 13 kinds of histological diagnosis. Bikunin immunoreactivity was detected in all of the brain tumors examined. Fibrillary staining of the glial processes was observed in astrocytoma, oligodendroglioma, and schwannoma. Intracytoplasmic staining in the interstitial cells, reactive astrocytes, and macrophages was noted in medulloblastoma, ependymoma, and meningioma. Metastatic tumors demonstrated intense immunoreactivity in the tissues surrounding the tumor cells. Neuronal cells revealed no bikunin immunoreactivity. There was no correlation between the intensity of staining and histologic type or grading of malignancy. In view of our earlier report that bikunin was present in the connective tissues around the site of cancer invasion, the above findings suggest that bikunin may play an important role in defense or repair at the tissue destruction and degeneration site.