Ventriculolumbar perfusion chemotherapy with methotrexate (MTX) and cytosine arabinoside (Ara-C) was performed in six patients with meningeal dissemination of malignant disease. Ten mg of MTX and 40 mg of Ara-C were injected via Ommaya reservoir every 12 hours for 3 days. During perfusion, we observed nausea and vomiting, low grade fever, confusion, nystagmus, paresthesia or numbness of the lower extremities, and multicranial nerve impairment, which disappeared soon after perfusion chemotherapy. After treatment, one patient developed bacterial meningitis, and two developed MTX-induced interstitial pneumonitis, which was cured by steroid therapy. Signs and symptoms due to involvement of the cerebrum, cranial nerves and spinal cord or spinal roots, improved more than by standard intrathecal chemotherapy. Laboratory cerebrospinal fluid (CSF) findings, i.e., cell count and cytological appearance, also improved more than by standard intrathecal chemotherapy. EEG, CT scan and MRI data revealed a worsening of EEG findings in one patient, and a small lesion on MRI, which was not seen by CT scan, disappeared after treatment in two patients.