In a randomized postoperative trial, adjuvant post-irradiation chemotherapy, consisting of nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP), was tested versus radiation therapy alone for newly diagnosed medulloblastoma in patients between 1 and 21 years of age. Patients treated with irradiation plus MOPP had a statistically significant increase in overall survival rate at 5 years posttreatment compared to patients treated with radiation therapy alone (74% vs. 56%; p = 0.06, adjusted for race and gender). Although the overall study failed to show a statistically significant advantage for irradiation plus MOPP in event-free survival (p = 0.18), statistical significance was attained in children 5 years of age or older (p = 0.05). More severe hematological toxicities occurred in the group with irradiation plus MOPP; however, this hematotoxicity appeared to be tolerable and acceptable. These results suggest that patients may benefit from combined irradiation and chemotherapy following surgery for medulloblastoma.