OBJECTIVE:To investigate physiological and performance adaptations associated with extremely high daily sustained physical activity levels, we followed six runners participating in the 2015 Race Across the USA. Participants completed over 42.2 km a day for 140 days, covering nearly 5,000 km. This analysis examines the improvement in running speed and potential adaptation in mean submaximal heart rate (SHR) throughout the race. METHODS:Data were collected during three 1-week long periods corresponding to the race beginning, middle, and end and included heart rates (HRs), body mass, running distances and speeds. HR data were collected using ActiTrainer HR monitors. Running speeds and distances were also recorded throughout the entire race. RESULTS:Athletes ran significantly faster as the race progressed (p < .001), reducing their mean marathon time by over 63 min. Observed mean SHR during the middle of the race was significantly lower than at the beginning (p = .003); however, there was no significant difference between mean SHR at the middle and end of the race (p = .998). CONCLUSION:These results indicate an early training effect in SHR during the first half of the race, which suggests that other physiological and biomechanical mechanisms were responsible for the continued improvement in running speed and adaptation to the high levels of sustained physical activity.