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Abstract: Aims: This study investigated an adaptive threshold-based method to delineate the target volume using 18fluoro-2-deoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT) before and during a course of radical radiotherapy or chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck. Materials and methods: Ten patients were enrolled between March 2006 and May 2008. 18FDG PET/CT scans were carried out 72h before the start of radiotherapy and then at three time points during radiotherapy (8–18, 36–50 and 66Gy). Functional volumes were delineated using an adaptive iterative algorithm weighted according to the mean standard uptake value (SUVmean) within the region of interest. The background 18FDG uptake, maximum standard uptake value (SUVmax) and SUVmean within the volumes were assessed. Results: There was no significant reduction in the primary target volumes defined by the adaptive threshold during radiotherapy. However, the SUVmax significantly reduced within the primary (P =0.003–0.011) and lymph node (P <0.0001) target volume at 36–50 and 36–66Gy compared with 0Gy. The SUVmean was negatively correlated to radiation dose (P <0.0001–0.014). The ratio between the background uptake of 18FDG and the SUVmean significantly reduced for both the lymph node target volume at 36–50Gy and the primary volume at 66Gy. The lack of significant correlation between the defined volume and radiation dose was because the SUVmean within the region of interest used to define the edge of the volume was equal to or less than the background 18FDG uptake and the software was unable to effectively differentiate between tumour and background uptake. Conclusions: The adaptive threshold method may be of benefit when used to define the target volume before the start of radiotherapy. This method was not beneficial during radiotherapy because the software is not sensitive enough to distinguish tumour from background and define a volume. 18FDG PET/CT-guided volumes delineated by automatic adaptive thresholding methods should only be used for dose escalation with the pretreatment imaging. [Copyright &y& Elsevier]