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To determine the effect of a high-fat or high-carbohydrate diet and running wheel activity on body composition, body mass, and caloric intake in C57Bl/6 mice.At 4 wk of age, five groups of C57Bl/6 mice were housed individually. Two groups had running wheels, whereas the other three groups did not. Within the running wheel groups, FAT-W consumed a high-fat diet (60.3% fat) and CHO-W consumed a high-carbohydrate diet (70.4% carbohydrate). Within the nonrunning groups, FAT consumed the high-fat diet, CHO consumed the high-carbohydrate diet, and the fifth group consumed standard chow. All groups consumed food ad libitum and were exposed to their respective conditions for 12 wk. Wheel activity, food consumption, body mass (BM), and percentage of body fat (%BF) were recorded.There was no significant difference in %BF or BM at the end of 12 wk between FAT-W and FAT or between CHO-W and CHO (P > 0.05). %BF was significantly higher in both FAT-W (42.9% ± 0.6%) and FAT (45.9% ± 0.8%) compared with CHO-W (30.8% ± 1.4%) or CHO (33.4% ± 1.0%; P < 0.001). BM was significantly higher in both FAT-W (42.8 ± 0.7 g) and FAT (44.7 ± 1.2 g) compared with either CHO-W (32.8 ± 1.6 g) or CHO (37.1 ± 0.8; P < 0.01). There was no difference in wheel activity between FAT-W and CHO-W (P > 0.05). Daily caloric intake was higher in both FAT-W (17.0 ± 0.8 kcal) and FAT (15.9 ± 0.9 kcal) compared with that in CHO-W (13.9 ± 0.7 kcal) and CHO (13.6 ± 0.5 kcal; P < 0.01).Access to a running wheel had no protective effect on BM or %BF in C57Bl/6 mice that consumed either a high-fat or a high-carbohydrate diet during a 12-wk period. Access to a running wheel did not affect caloric intake; however, average daily caloric intake was higher in mice on high-fat diets compared with that in mice on a high-carbohydrate diet.