BACKGROUND We designed a protocol with the goal of improving the disease free and overall survival of patients with previously untreated Stage IV nasopharyngeal carcinoma (NP(C)). The regimen consisted of intensive induction chemotherapy followed shortly thereafter by radiation therapy. METHODS Between March 1986 and March 1992, 27 patients with T3-4, N2-3, M0 squamous cell carcinoma of the nasopharynx were treated with 2 cycles of chemotherapy, using cisplatin, 100 mg/m2 intravenously, on Day 1, and 5-fluorouracil (5-FU), 1000 mg/m2 per day continuous infusion, on Days 2-5. The second cycle was given on Day 16 and was followed by radiotherapy (RT), 70 Gray, given on Day 31. RESULTS The objective response rate to chemotherapy was 93%, with a 37% complete response (CR) rate and a 56% partial response (PR) rate. The overall CR rate after RT was 85%. With a median follow-up of 60 months, the overall actuarial survival rate was 66%. Patients who had a CR after chemotherapy had a superior survival probability (100%). Toxicity was tolerable, without lethal complications. CONCLUSIONS This study demonstrates that cisplatin/5-FU chemotherapy given in an intensive schedule and followed shortly thereafter by radical RT can improve the CR rate and survival of patients with locally advanced NPC, with tolerable toxicity.