Recurrent and progressive non-GBM gliomas are a diverse group of brain tumors that often respond poorly to adjuvant chemotherapy treatment. Regional intra-arterial (IA) administration of chemotherapy may result in increased tumor uptake of drug, with improvement in response rates and time to progression (TTP). Twenty-five patients with recurrent or progressive non-GBM gliomas were treated with IA carboplatin (200 mg/m2/d) and intravenous (IV) etoposide (100 mg/m2/d) for 2 days every 4 weeks. Patients ranged in age from 22 to 68 years (mean 37.8). All but one patient had received standard irradiation, and eight patients had attempted prior chemotherapy. Five of 25 patients had objective responses (20%), while another 15 patients had stable disease (60%), receiving a total of 318 IA treatment procedures. There was one complete response (4.0%), three partial responses (12.0%), one minor response (4.0%), 15 stable diseases (60.0%), and five progressive diseases (20.0%). The median TTP was 24.2 weeks overall and 32 weeks in responders. Overall median survival was 34.2 weeks. Therapy was well tolerated, with mainly hematologic toxicity. Two patients had embolic complications. Although these are preliminary results, IA carboplatin and IV etoposide have modest activity against recurrent and progressive non-GBM gliomas and warrants further study.