In order to improve loco-regional control in locally advanced oropharyngeal carcinoma, a phase II trial was designed to establish the feasibility of concomitant conventional radiotherapy and three cycles of chemotherapy at day 1, 21 and 42 with cisplatin (CDDP) 20 mg/m2 and 5-fluorouracil (5-FU) 400 mg/m2 day 1 to day 4, and mitomycin C (MMC) 10 mg/m2 day 1. From March 1990 to September 1993, 27 patients (mean age: 55) were included in this study. Three patients (11%) were T2N0, 19 (70%) T3 (T3N0: n = 9, T3N1: n = 1, T3N2: n = 5, T3N3: n = 4), and 5 (19%) T4 (T4N0: n = 1, T4N1: n = 1, T4N2: n = 2, T4N3: n = 1). With a mean follow-up of 34 months (17-59), ten patients (37%) were alive, free of disease; among the 17 other patients, seven died with cancer. Loco-regional control rate was 85%. One and 2-year survival rates were respectively 48 and 31% for overall and disease-free survival; respective corrected overall survival rates were 68 and 61%. Grade 3 or 4 mucositis was 81%; enteral feeding was necessary for 63% of the patients; mean loss of weight was 5.7 kg. Grade > 2 thrombopenia occurred in 11 patients (41%), grade > 2 neutropenia in eight patients (29%) , grade > 2 anemia in four patients (15%). Febrile neutropenia or aplasia occurred in five patients (19%). Two patients (7%) died during treatment of haematological or infectious complications related to the treatment. Another patient died 2 months after treatment with grade 4 thrombopenia and septicemia. Addition of MMC to 5-FU and CDDP might have been partly responsible of this increased toxicity. A high complete response rate has been achieved with this concomitant radio-polychemotherapy, but with a severe digestive and haematological toxicity, which did not allow to conclude to the feasibility of this therapeutic association.