The mediators of the perception of effort during exercise are still unclear. The aim of the present study was to examine physiological responses during runs using a rating of perceived exertion (RPE)-clamp model at the RPE corresponding to the gas exchange threshold (RPE) and 15% above GET (RPE) to identify potential mediators and performance applications for RPE during treadmill running.Twenty-one runners ([Formula: see text] = 51.7 ± 8.3 ml kg min) performed a graded exercise test to determine maximal oxygen consumption and the RPE associated with GET and GET + 15% followed by randomized 60 min RPE-clamp runs at RPE and RPE. Mean differences for [Formula: see text], heart rate (HR), minute ventilation ([Formula: see text]), respiratory frequency ([Formula: see text], respiratory exchange ratio (RER), and velocity were compared across each run.After minute 14, [Formula: see text], RER and velocity did not differ across conditions, but decreased across time (p < 0.05). There was a significant (p < 0.05) condition × time interaction for [Formula: see text], where values were significantly higher during RPE-clamp runs at RPE and decreased across time in both conditions. There were no differences across condition or time for HR, and only small difference between conditions for [Formula: see text].HR and [Formula: see text] may play a role in mediating the perception of effort, while [Formula: see text], RER, and [Formula: see text] may not. Although HR and [Formula: see text] may mediate the maintenance of a perceptual intensity, they may not be sensitive to differentiate perceptual intensities at GET and GET + 15%. Thus, prescribing exercise using an RPE-clamp model may only reflect a sustainable [Formula: see text] within the moderate intensity domain.