The purpose of this study is to evaluate the effect of tumor volume and radiotherapy on the uptake of 18F-2-fluoro-2-deoxy-D-glucose (18FDG). The tumor models used were mouse mammary carcinoma MM48, FM3A, and rat hepatoma AH109A. Results were expressed as an 18FDG uptake ratio. This was the ratio of irradiated tumor uptake of 18FDG to unirradiated tumor uptake. The total tumor uptake was expressed as 18FDG uptake ratio multiplied by relative tumor volume. Following 20 Gy irradiation of the radioresistant tumor (MM48), the 18FDG uptake ratio was found to be unchanged, whereas in radiosensitive tumors (FM3A) the 18FDG uptake ratio was 0.37, the relative tumor volume was 0.31, and the calculated total tumor uptake was 0.11 on the eighth day after irradiation. The total tumor uptake was lower than the relative tumor volume. AH109A began to regrow after ten Gy irradiation, accompanied by elevated uptake of 18FDG on the seventh day. These results suggest that the 18FDG uptake by tumor is a good marker of radiotherapeutic effects as well as relapses of cancers and is more sensitive than morphological methods.