The aim of the study was to test whether the addition of three cycles of chemotherapy during standard radiation therapy would improve disease-free survival in patients with stages III and IV oropharynx carcinoma. A total of 226 patients have been entered in a phase III multicentric randomized trial comparing radiotherapy alone (arm A) to radiotherapy with concomitant chemotherapy (arm B). Radiotherapy was identical in the two arms, delivering, with conventional fractionation, 70 Gy in 35 fractions. In arm B patients received simultaneously 3 cycles of a four-day regimen containing carboplatin (70 mg/m2/d) and 5 fluorouracil (600 mg/m2/d) continuous infusion. The two arms were equally balanced regarding to age, gender, stage, performance status, histology, and primary tumor site. Radiotherapy compliance was similar in the two arms regarding to total dose, treatment duration and treatment interruption. Grade 3 and 4 mucositis rate was significantly higher in arm B (67% versus 36%). Skin toxicity was not different. Haematologic toxicity was higher in arm B on neutrophil count and hemoglobin level. Three-year overall actuarial survival and disease-free survival rates were respectively 51% versus 31% and 42% versus 20% for patients treated with combined modality versus radiation alone (p = 0.022 and 0.043). Local and regional control rate has been improved in arm B (66% versus 42%). The statistically significant improvement in overall survival obtained support the use of concomitant chemotherapy as an adjunct to radiotherapy in the management of carcinoma of the oropharynx.