PURPOSE Because of the high rates of local tumor control obtained by combining moderate doses of external beam radiotherapy and synchronous 5-fluorouracil/mitomycin C chemotherapy in the treatment of squamous and basiloid cancers of the anal canal, we chose to investigate this regimen for nasopharyngeal cancer which shows significant local and distant failure rates after treatment with radiotherapy alone. METHODS AND MATERIALS Between 1983 and 1990, 43 patients with previously untreated squamous cell and undifferentiated nasopharyngeal cancer, without evidence of distant metastases at diagnosis were treated with radical radiotherapy and concurrent chemotherapy using mitomycin C (10 mg/m2 i.v. day 1 of radiotherapy) and 5-fluorouracil (1000 mg/m2 continuous i.v. infusion days 1-4 of radiotherapy and repeated at least 28 days later). Ninety-one percent of cases had Stage IV tumors and 93% had clinically involved regional lymph nodes. RESULTS Actuarial rates of survival, local control, regional nodal control and distant metastases at 5 years were 37%, 71%, 94%, and 53%. Grade 3 or 4 skin and mucosal reactions occurred in 30% and 34% of patients, respectively. Only one patient developed greater than Grade 2 myelosuppression and he died of overwhelming sepsis. A second patient died of malnutrition 4 months after treatment giving a 5% incidence of treatment-related mortality. Nine percent of patients developed significant late complications of treatment. CONCLUSION Despite the morbidity observed, the treatment outcome is not obviously superior to that reported for radiotherapy as a single modality of treatment.