BACKGROUND: Studies in rodents have shown that brown adipose tissue (BAT) is activated on food intake, thereby reducing metabolic efficiency. OBJECTIVE: The current study investigated whether a single high-calorie, carbohydrate-rich meal activates BAT in lean human adults. DESIGN: BAT activity was studied in 11 lean adult men [age: 23.6 +/- 2.1 y; body mass index (BMI; in kg/m2): 22.4 +/- 2.1] after consumption of a high-calorie, carbohydrate-rich meal (1622 +/- 222 kcal; 78% carbohydrate, 12% P, 10% F). BAT activity during 2 h of mild cold exposure served as a positive control experiment. BAT activity was assessed by [18F]fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography. Energy expenditure was measured by indirect calorimetry. RESULTS: Postprandial [18F]FDG uptake was significantly higher in BAT [1.65 +/- 0.99 mean standard uptake value (SUVmean)] than in subcutaneous (0.35 +/- 0.15 SUVmean; P < 0.05) and visceral (0.49 +/- 0.24 SUVmean; P < 0.05) white adipose tissue and liver (0.95 +/- 0.28 SUVmean; P < 0.05). Postprandial BAT activity was lower than cold-induced BAT activity (7.19 +/- 2.09 SUVmean). However, postprandial BAT activity may have been underestimated because of high postprandial [18F]FDG uptake in skeletal muscle compared with cold (1.36 +/- 0.31 compared with 0.59 +/- 0.07 SUVmean, P < 0.05), which reduces [18F]FDG bioavailability for BAT and other tissues. No direct relation was found between BAT and diet-induced thermogenesis (DIT). CONCLUSIONS: Glucose uptake in BAT increases after a meal in humans, which indicates a role for BAT in reducing metabolic efficiency. However, the quantitative contribution of BAT to DIT relative to other tissues, such as skeletal muscle, remains to be investigated. This trial was registered at www.controlled-trials.com as ISRCTN21413505.