Chemotherapy has been rarely considered an important treatment modality for brain metastases. Based on the hypothesis that the lack of efficacy of chemotherapy, rather than the blood-brain barrier itself, may be the major hindrance to the successful chemotherapeutic treatment of brain metastases, we started a trial in which a selected group of non-small cell lung cancer patients with brain metastases received primary treatment with systemic chemotherapy. The treatment consisted of three courses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 225 mg/m2 given intravenously over 3 hours and carboplatin dosed to an area under the concentration-time curve of 6, with close monitoring of the lesion by computed tomography or magnetic resonance imaging of the brain after each chemotherapy course. Any radiographic or clinical evidence of progression in the brain during treatment or no improvement in the brain after three cycles of chemotherapy mandated whole brain irradiation (30 Gy in 10 fractions). Responding patients received three additional courses of chemotherapy; whole brain irradiation was given after completion of all six chemotherapy cycles. To date, five patients have been enrolled, and one has achieved partial remission both in the brain and at the extracranial site. Other patients did not achieve major objective responses either in the brain or at the extracranial sites. These preliminary results, which are consistent with the study hypothesis, support the feasibility of our approach. We therefore continue to accrue patients for this study.