Some people remain lean despite pressure to gain weight. Lean people tend to have high daily activity levels, but the source of this increased activity is unknown. We found that leanness cannot be accounted for by increased weight-corrected food intake in two different types of lean rats. As previously reported in lean people, we found that lean rats had higher daily activity levels; lean rats also expended more energy. These lean rats were developed through artificial selection for high aerobic endurance capacity. To test whether our findings extended to a human population, we measured endurance capacity using a VO(2max) treadmill test and daily activity in a group of non-exercising individuals. Similar to lean rats selectively bred for endurance capacity, our study revealed that people with higher VO(2max) also spent more time active throughout the day. Hence, endurance capacity may be the trait that underlies both physical activity levels and leanness. We identified one potential mechanism for the lean, active phenotype in rats, namely high levels of skeletal muscle PEPCK. Therefore, the lean phenotype is characterized by high endurance capacity and high activity and may stem from altered skeletal muscle energetics.