The aim of the present investigation was to test the hypothesis that long-term modulation (LTM) of the exercise ventilatory response, evidenced as an augmentation in minute ventilation (V(I)) and tidal volume (VT) during the early phase of exercise, is only evident when the muscle groups recruited are the same during testing and during hypercapnic exercise conditioning. Measurements of cardiorespiratory variables were made at rest and during leg cycling (fH=107+/-5) exercise in eight male subjects, 1 week before and 1 h after conditioning. Conditioning involved either: (a) ten trials of arm cranking exercise (V(I)=29.0+/-4.4), or (b) ten trials of arm cranking exercise paired with external respiratory dead space (1400 ml; V(I)=57.3+/-6.5). Neither arm conditioning paradigm evoked any of the modulatory responses described in previous studies. We, therefore, conclude that the general upregulation of the spinal respiratory motoneuron pool excitability after conditioning (the "final common pathway" hypothesis), may be inadequate to fully explain the underlying mechanisms of LTM of ventilation in humans.