Vagal modulation of chemical control of ventilation during rest and exercise was studied in 15 anesthetized mongrel dogs. Arterial chemical stimuli--hypoxic, hypercapnic or a combination of both, increased ventilation by increasing both rate and depth of breathing during rest and exercise in the intact dogs. After bilateral vagotomy chemical drive increased ventilation mostly by depth and little by rate. The ventilatory response to the chemical drive, therefore, reached a plateau when tidal volume approached its maximal value ata relatively unchanged breath frequency. Muscular exercise, however, largely restored frequency response in the vagotomized animals. Since the rate response to chemical stimuli but not to exercise was impaired by vagotomy, we concluded that hyperpnea of exercise could occur through a mechanism not shared by the chemical control of ventilation. The relationship between tidal volume and breath cycle during chemical stimulation was modulated by the volume related vagal reflex. During exercise, another mechanism, presumably bulbo-pontine, is activated to influence the relationship independent of the lung volume.