The aim of this study was to compare CT, MRI and FDG-PET in the prediction of outcome of neoadjuvant radiochemotherapy in patients with locally advanced primary rectal cancer. A total of 23 patients with T3/4 rectal cancer underwent a preoperative radiochemotherapy combined with regional hyperthermia. Staging was performed using four-slice CT (n=23), 1.5-T MRI (n=10), and (18)F-FDG-PET (n=23) before and 2-4 weeks after completion of neoadjuvant treatment. Response criteria were a change in T category and tumour volume for CT and MRI and a change in glucose uptake (standard uptake value) within the tumour for FDG-PET. Imaging results were compared with those of pretherapy endorectal ultrasound and histopathological findings. Histopathology showed a response to neoadjuvant therapy in 13 patients whereas 10 patients were classified as nonresponders. The mean SUV reduction in responders (60+/-14%) was significantly higher than in nonresponders (37+/-31%; P=0.030). The sensitivity and specificity of FDG-PET in identifying response was 100% (CT 54%, MRI 71%) and 60% (CT 80%, MRT 67%). Positive and negative predictive values were 77% (CT 78%, MRI 83%) and 100% (CT 57%, MRI 50%) (PET P=0.002, CT P=0.197, MRI P=0.500). These results suggest that FDG-PET is superior to CT and MRI in predicting response to preoperative multimodal treatment of locally advanced primary rectal cancer.