PURPOSE: This study examined the intensity (velocity), metabolic (VO2), respiratory (minute ventilation [VE] and breathing frequency [fb]), and neuromuscular (electromyographic amplitude [EMG AMP] and EMG mean power frequency [MPF]) factors that may underlie the perception of effort (rating of perceived exertion [RPE]) during constant heart rate (HR) running within the heavy exercise intensity domain. METHODS: Eight runners (mean ± SEM; age = 24 ± 1 years) completed an incremental test to exhaustion for the determination of the gas exchange threshold (GET), respiratory compensation point (RCP), heart rate peak (HRpeak), and peak oxygen consumption rate (VO2peak). The RPE, velocity, VO2, VE, fb, EMG AMP, and EMG MPF responses were recorded during a constant HR run (88.3 ± 1.1 %HRpeak; 78.9 ± 2.1 % VO2peak) within the heavy exercise intensity domain at 50% of the difference between the GET and RCP. The relationships for each variable versus time were examined using polynomial regression models (linear and quadratic) at an alpha level of p ≤ 0.05. RESULTS: During the constant heart rate run, the subjects reached the selected HR within 1.83 – 5.00 min and maintained the run for 57.17 ± 0.4 min. The mean percent changes from the time the HR was reached to the end of the run for RPE, velocity, VO2, VE, fb, EMG AMP, and EMG MPF were 9.0 ± 8.1%, -23.3 ± 1.4%, -12.1 ± 2.1%, -18.4 ± 2.1%, 15.8 ± 5.7%, -10.0 ± 4.9%, and 5.1 ± 3.5%, respectively. The polynomial regression analyses indicated there was no change in HR (r2 =0.20), but quadratic increases in RPE (R2 =0.88) and fb (R2 =0.87) as well as a linear increase in EMG MPF (R2 =0.65). In addition, there were quadratic decreases in velocity (R2 =0.90), VO2 (R2 =0.95), and VE (R2 =0.94) as well as a linear decrease in EMG AMP (r2 =0.74). CONCLUSION: These findings indicated that during constant HR running within the heavy exercise intensity domain, increases in RPE were associated with fb and EMG MPF, but dissociated from HR, velocity, VO2, VE, and muscle activation (EMG AMP), which remained constant or decreased. It is possible the RPE was influenced by afferent signals from the respiratory muscles associated with fb and/or sensory cues from increases in muscle/core temperature typical of prolonged (>20 min) exercise within the heavy domain. Supported by the 2013 NSCA Doctoral Research Grant.