Twenty-eight patients with malignant brain tumors (16 with primary brain tumors and 12 with brain metastases) progressing after cranial irradiation with or without chemotherapy received varying doses of intracarotid VP-16. Courses of therapy were repeated every 4 weeks along with computerized axial tomography scan and neurologic examination. Of 15 evaluable patients with primary malignant brain tumors, 1 responded to therapy and 5 had no immediate tumor progression for 2-10 months. None of 12 evaluable patients with brain metastases responded to intracarotid VP-16 although 5 had no immediate tumor progression from 1-4 months. Side effects of treatment were uncommon. Using this route of administration, intracarotid VP-16 does not appear to increase response rates in patients with primary malignant brain tumors, compared with results reported for intravenous VP-16.