To assess whether therapeutic efficacy is related to the intra-arterial (IA) mannitol infusion prior to ACNU and cisplatin (CDDP) for malignant brain tumors, the survival time of patients with and without mannitol infusion was compared. Ninety-eight patients were randomly assigned to either a mannitol infusion group (group A) or a non-mannitol infusion group (group B); 34 with malignant gliomas (18 in group A and 16 in group B) and 64 with brain metastases (36 in group A and 28 in group B). During radiotherapy, ACNU and CDDP at a dose of 100 mg/body were given through the common carotid artery at a rate of 20 mg/min. In group A, 50 ml of 20% mannitol was injected intra-arterially at a rate of 50 ml/min immediately prior to the injection of chemotherapeutic agents. Of the patients with malignant gliomas, the median survival time (MST) was 52 weeks for all 34 cases, 68 weeks for group A, and 47 weeks for group B. Survival analysis showed no significant differences between the two treatment groups. Of the patients with brain metastases, the MST was 40 weeks for all 64 cases, 47 weeks for group A, and 24 weeks for group B; the survival time was significantly longer in group A as compared to group B (p < 0.05). This study has demonstrated that, for the patients with brain metastases, IA mannitol infusion provided a survival benefit in the IA chemotherapy employing ACNU and CDDP. In contrast, IA mannitol infusion offered no survival benefit to the patients with malignant gliomas.