A Phase I/II clinical trial was undertaken between January 29, 1987 and January 25, 1997 to assess the efficacy of (125)I-labeled monoclonal antibody 425 ((125)I-MAb 425) in controlling high-grade brain gliomas. A total of 180 patients diagnosed with glioblastoma multiforme (GBM) and astrocytoma with anaplastic foci (AAF) were administered (125)I-MAb 425 as an adjuvant treatment. All underwent initial surgery followed by postoperative external beam radiation therapy and a cumulative dose of 140 mCi of (125)I-MAb 425. Biodistribution of radioactivity after antibody administration showed increased uptake in brain tumor cells due to enhanced expression of epidermal growth factor receptors. A longer half-life of (125)I-MAb 425 in brain tumor cells compared to blood was observed. All patients were followed up for at least 5 years. Overall actuarial survival range for GBM and AAF patients showed 4-150 and 4-270 months, respectively. GBM and AAF patients under age 40 years with a Karnofsky performance status >70 had an actuarial median survival of 22.5 and 65 months, respectively. This adjuvant therapy demonstrates a significant increase in median survival and should be considered in the management of high-grade brain gliomas.