The role of radiation therapy in the treatment of supratentorial oligodendrogliomas is controversial. To evaluate the role of radiation therapy, the Duke University Medical Center series was retrospectively analyzed. Clinical history, radiation dosages, and pathologic materials were reviewed. Seventy-one patients were identified as having histologically proven oligodendroglioma. Analysis of the patient population demonstrated it to be similar in all major parameters to other populations previously reported in the literature. Multivariate statistical analysis of the demographic, clinical and radiographic variables of these patients showed that a poorer prognosis was associated with persons of increased age (P = 0.052) and black persons (P = 0.014), and in those with papilledema (P = 0.07), hemiparesis (P = 0.001), intellectual deficits (P = 0.0002), and necrosis (P = 0.041). All patients had a surgical procedure as first treatment while 18 and three patients, respectively, underwent a second and third surgical procedure. Thirty-seven patients had a subsequent course of radiotherapy. Univariate and multivariate statistical analysis comparing the patients treated with surgery alone those treated with surgery plus radiotherapy revealed no significant population or prognostic differences between the groups. The median times until clinical deterioration were 39 versus 27 months, the median times until documented tumor recurrence were 27 versus 28 months and the median survival times were 4.5 versus 5.2 years, for nonirradiated versus irradiated patients. These data, from a large and rigidly evaluated population, demonstrated no statistically significant difference in the symptom-free interval, time until tumor recurrence, or survival between the groups nor did radiation appear beneficial to any subgroup evaluated. The results suggest the need for a prospective clinical trial to evaluate the true role of radiation therapy in the treatment of this tumor.