PURPOSE: This study aimed at assessing the value of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) for predicting the response of locally advanced rectal cancer to neoadjuvant CRT. MATERIALS AND METHODS: Between August 2006 and January 2008, we prospectively enrolled 20 patients with locally advanced rectal cancer and who were treated with neoadjuvant CRT at the Korea Institute of Radiological and Medical Sciences. The treatment consisted of radiation therapy and chemotherapy, and this was followed by curative resection 6 weeks later. All the patients underwent 18F-FDG PET/CT both before CRT and 6 weeks after completing CRT. The measurements of the FDG uptake (SUV(max)), the absolute difference (DeltaSUV(max)) and the percent SUV(max) difference (response index, RI(SUV)) between the pre- and post-CRT 18F-FDG PET/CT scans were assessed. The measurements of the metabolic volume, the absolute difference (Delta metabolic volume) and the percent metabolic volume difference (response index, RI(metabolic volume)) were also assessed. RESULTS: Of the 20 patients who underwent surgery, 11 patients (55%) were classified as responders according to Dworak's classification. The post-CRT SUV(max) was significantly lower than the pre-CRT SUV(max). However, there were no significant differences in the SUV(max) and the metabolic volume reduction between the responders and non-responders. We used a minimum SUV(max) reduction of 67% as the cut-off value for defining a response, with a sensitivity of 45.5%, a specificity of 88.9%, a positive predictive value of 77% and a negative predictive value of 53.8%. CONCLUSION: Although there were no statistically significant results in this study, other studies have revealed that 18F-FDG PET/CT has the potential to assess the tumor response to neoadjuvant CRT in patients with locally advanced rectal cancer.