The purpose of this study was to determine the efficacy of 24-hour concomitant infusions of etoposide (100 mg/m2/day, days 1-3) and cisplatin (45 mg/m2/day, days 2-3) in the treatment of patients with recurrent astrocytoma. All 36 patients entered on this trial had histologic proof of astrocytoma with CT scan evidence of tumor progression despite prior radiotherapy and nitrosourea chemotherapy. At initial diagnosis, three patients had low-grade astrocytoma, but 33 (92%) had high-grade astrocytomas. ECOG performance score was 0-1 in 20 patients and 2-3 in 16 patients. The median age of all patients was 45.5 years. Dose-limiting toxicity was myelosuppression with median leukocyte and platelet nadirs of 2,150/mcL and 56,500/mcL respectively. One life-threatening infection occurred, but there were no treatment-related deaths. Vomiting occurred in 78% of patients, but was severe in only 6%. Peripheral neuropathy occurred in 28% but was severe in only 6%. Six patients (17%; 1 CR, 5 REGR) responded to therapy with median time to progression of 6.0 months (range 1.5-17.7 months). Five additional patients (14%) remained stable greater than 6 months and 1 has not progressed at 17.0+ months. Median time to progression and survival in all patients were 2.7 and 5.8 months, respectively. In conclusion, etoposide and cisplatin at this dose and schedule have limited activity in the treatment of recurrent high grade astrocytomas, although durable responses or periods of stability occurred in some patients. Considering the extent of myelosuppression, near maximal doses of the drugs were given.