Nineteen patients with malignant head and neck tumors were imaged before and during radiation therapy with 18F-2-fluoro-2-deoxy-D-glucose (FDG) to study the effect of radiotherapy (RT) on FDG uptake. All tumor images were FDG-positive before treatment. After RT, a decrement of tumor FDG uptake was found in all but two patients; these were nonradioresponders. There was a significant decrement (p less than 0.001) in uptake ratios after irradiation of 30 +/- 5 Gy among the radioresponsive (CR + PR) but not among the radioresistant (NC + PD) tumors. The administered dose of RT correlated (r = 0.47, p less than 0.05) with the decrement in FDG activity among the CR + PR but not among the NC + PD patients. The biologic half-life of FDG radioactivity in tumor tissue was evaluated by dynamic scintigraphy. A change in the half-life of FDG toward the value observed in normal tissue was associated with treatment response. The results suggest that FDG imaging can be used for follow-up of RT in patients with head and neck cancer.