Arterial isocapnia is a hallmark of moderate exercise in humans, and is maintained even when resting arterial (PCO₂) PaCO₂ is raised or lowered from its normal level, e.g. with chronic acid-base changes or acute increases in respiratory dead space. When resting ventilation and/or PaCO₂ are altered, maintenance of isocapnia requires active adjustments of the exercise ventilatory response (slope of the VE-VCO₂ relationship, VE/VCO₂). Based on animal studies, it has been proposed that a central neural mechanism links the exercise ventilatory response to the resting ventilatory drive without need for changes in chemoreceptor feedback from rest to exercise, a mechanism referred to as short-term modulation (STM). We tested the hypothesis that STM is elicited by increased resting ventilatory drive associated with added external dead space (DS) in humans. Twelve young men were studied in Control conditions and with added DS (200, 400 and 600 ml; randomized) at rest and during mild-to-moderate cycle exercise. VE/VCO₂ increased progressively as DS volume increased (p<0.0001). While resting end-tidal PCO₂ (PETCO₂) increased with DS, the change in PETCO₂ from rest to exercise was not increased, indicating that increased chemoreceptor feedback from rest to exercise cannot account for the greater exercise ventilatory response. We conclude that STM of the exercise ventilatory response is induced in young men when resting ventilatory drive is increased with external DS, confirming the existence of STM in humans.