This study sought to examine the exercise-induced ST-segment shifts, J₀ and J₆₀, attributable to ECG lead configuration, specifically to evaluate if ischemic changes are modified as a function of using the Mason-Likar lead system. Males (N=30) referred for diagnostic testing underwent a symptom-limited graded exercise test (SLGXT). ST-segment shifts, J₀ and J₆₀, measured as the difference from baseline to recovery minute one, were not significantly different in responses measured from two simultaneous complexes for lead V₅. In frontal lead II, differences were found in the ST-segment response at baseline vs. recovery minute one. All ST-segment shifts were computed as the difference between J_x obtained at resting baseline vs. the J_x obtained at the exercise measurement in the same posture. ST-segment shifts, J₀ and J₆₀, measured at peak-exercise vs. recovery minute one using the Mason-Likar lead system, revealed a significant difference according to the measurement recorded in both leads V₅ and II (p<.05). Comparisons of frequencies for clinically abnormal ST-segment shifts according to ECG lead configuration at recovery minute one when measured from peak-exercise using Mason-Likar were significant in only lead II (p<.05). Observation of the data suggest that the Mason-Likar lead system may affect the interpretation of ischemic ST-segment shifts in lead II. However, these results do not invalidate the interpretation of ischemic ST-segment shifts in lead V₅ using the Mason-Likar lead system.