The outcome of therapy is reported in 34 previously untreated patients with advanced-stage (AJC IV) nasopharyngeal carcinoma treated with combination chemotherapy (cisplatin and non-cisplatin based) and sequential radiation therapy. Sixty-nine patients treated with radiotherapy alone were used as a control group. The control group was matched for T and N stage grouping but differed in that 45% had keratinizing squamous carcinoma, 14.5% had nonkeratinizing squamous carcinoma, and 40.6% had undifferentiated carcinoma, compared with 18%, 50%, and 32.4%, respectively in the combined-treatment group. Seventeen of 21 patients (81%) who received chemotherapy followed by radiotherapy achieved complete remission (CR), whereas 11 of 13 patients (85%) who received radiotherapy followed by chemotherapy achieved CR (P = NS). Patients treated by radiotherapy alone had a 91% CR rate. The combined treatment yielded a relapse-free rate of 78% versus 44% for the radiotherapy group (P = 0.001). Median survival in the combined-treatment group has not been reached (111+ months), compared with 67 months in the group receiving radiotherapy alone (P = 0.04). The recurrence rate at the primary site and in regional nodes was more frequent in the radiotherapy group (36%), compared with the combined-therapy group (7%) (P = 0.004), but the occurrence of distant metastases was similar in each group (P = 0.41). The acute toxicity of the treatment was well tolerated. The major long-term toxic effect experienced by patients in the combined-therapy group was soft tissue fibrosis. These data suggest that a prospective trial comparing chemotherapy and radiotherapy versus radiotherapy alone is warranted.