Thirty-seven patients with recurrent primary brain tumors were treated with oral melphalan at a dose of 8 mg/m2/day for 5 days every 4-6 weeks. All patients had failed prior nitrosourea-based chemotherapy. Oral melphalan had no activity against glioblastoma, and minimal activity against other anaplastic astrocytomas. One recurrent medulloblastoma did have a clinical and radiographically sustained response that continued for greater than 14 months. We concluded that oral melphalan was not effective in the treatment of recurrent astrocytomas, but might have efficacy in medulloblastoma.