Positron emission tomography (PET) is a biochemical-imaging tool that uses the uptake of the glucose analog 2-deoxy-2-[F-18] fluoro-D-glucose (FDG) to detect head and neck tumor proliferation. The aim of this study is to determine if quantitation of either primary tumor metabolic activity or tumor response using PET scans could predict local control and overall survival in patients with head and neck cancer undergoing primary radiotherapy. Twelve patients with squamous cell carcinomas of the head and neck underwent PET scans before and 6 weeks after completion of radiation therapy. Tumor metabolic activity was quantitated using the metabolic ratio method. Mean follow-up was 40 months (range: 18-55 months). In our series, tumors with metabolic rates greater than that of the cerebellum are associated with significantly better local control (p < 0.05) and survival. Posttreatment PET imaging was falsely positive in one patient with clinical signs of severe inflammation. Tumors with greater than 50% decrease in metabolic activity with irradiation had improved local control. Clinically, nine patients had excellent response to irradiation. These results suggest that pretreatment PET findings may have prognostic implications in determining which patients will achieve long-term local control with primary radiation therapy. This may help identify those at increased risk of recurrence that may benefit from more aggressive altered fractionation schemes or combined modality therapy.