In order to investigate early changes in the glucose metabolism of irradiated tumours, tumour uptake of 2-[18F]fluoro-2-deoxy-d-glucose (18FDG) was studied in human tumour xenografts. Three human tumour lines [ependymoblastoma (NNE), small cell lung cancer (GLS), and glioblastoma (KYG)] showing different radiosensitivities and incidences of radiation-induced apoptosis were subcutaneously transplanted into nude mice, and were irradiated at a single dose of 10 Gy. Then 0.5 mCi of 18FDG was intravenously administered 1 h before sacrifice. The animals were sacrificed at 2, 4 and 6 h following irradiation, and 18FDG accumulation in the tumours was examined. Before irradiation, GLS and KYG tumours showed significantly higher rates of 18FDG accumulation compared with NNE tumours (P <0.004 and P <0.001, respectively). NNE (the most radiosensitive tumour with the highest incidence of radiation-induced apoptosis), however, displayed a 2.3-fold higher rate of 18FDG accumulation at 2 h following irradiation compared with a non-irradiated group (P <0.01), and thereafter showed a plateau up to 6 h. The accumulation did not increase significantly in the other tumours with lower radiosensitivity and much less radiation-induced apoptosis. The rapidity of the increase in 18FDG accumulation in the most radiosensitive tumour line, occurring as early as 2 h following irradiation, suggests that the increase was independent of recovery phenomena following radiation damage.