Empirical evidence in the clinical literature suggests that ionizing radiation influences human epileptic behavior. A group of patients with tumor-associated epilepsy, biopsy-proven malignancy, and primary antineoplastic treatment with ionizing radiation was selected to evaluate this observation. The antiepileptic effect of ionizing radiation was examined in 9 patients presenting with malignant cerebral tumor and medically refractory partial seizures during at least 2 months. Tissue diagnosis was obtained by stereotactic biopsy without further surgery. Histological categories included anaplastic astrocytoma (5 cases), glioblastoma (2), lymphoma (1), and metastatic non-small cell carcinoma of the lung (1). All patients had medically refractory simple partial seizures with or without secondary generalization with frequencies of 3/week to 8/day for 2-7 months before completion of therapy. Fractionated radiation therapy by parallel opposed fields was delivered with a cumulative dose range of 3,000-6,600 cGy. One patient also had 125I brachytherapy with implant removal after 6 months. Five patients had a seizure-free outcome for periods lasting 2-12 months, whereas the remainder experienced a reduction in frequency of greater than 75% during a follow-up period of 3 months to 6 years. One patient with a glioblastoma remained seizure-free for 3 months and experienced 2 generalized seizures during tumor progression and clinical deterioration but otherwise remained under good anticonvulsant control until his death after 1 year. This review of cases of partial seizures attributable to an unresected malignant cerebral tumor indicates that ionizing radiation may have a favorable effect upon medically refractory partial seizures with significant reduction or elimination of seizures. Moreover, the effect lasts beyond the immediate and early postradiation period. The therapy may thus also lessen the propensity for cerebral tissue towards later epileptogenicity that gives rise to a partial seizure disorder.