We investigated the physiologic heart rate (HR) to work rate (WR) relation throughout peak exercise in normal subjects as a guideline for rate-adaptive pacemaker slope programming. The study group consisted of 41 middle-aged subjects (22 men and 19 women) without evidence of cardiopulmonary disease. Peak-exercise stress tests were performed on a calibrated treadmill by usina the symptom-limited “ramping incremental treadmill exercise” (RITE) protocol. The HR response, oxygen uptake, and treadmill workload increments were assessed simultaneously. The HR/WR slope, as determined using linear regression analysis, was 0.37 ± 0.13 beats/min/W for the entire study group, which indicates an upper range increase of 5 beats/10 W increase of external treadmill work performed, using the mean value ±1 SD. Men generated an HR/WR slope of 0.32 ± 0.09 beats/min/W, and women, 0.43 ± 0.15 beats/min/W, indicating a significant sex-related difference in the HR/WR relation (p < 0.01). Thus, to achieve an appropriate matching or HR with patient effort, rate-adaptive pacemakers should generate an average increase of approximately 5 beats per increase in 10 W of external treadmill work. The HR/WR relation can easily be determined to provide the clinician with a minimal check system to avoid a hyper- or hypochronotropic paced response to exercise.