We investigated the effects of increasing CO2 ventilatory drive on the coordination of respiration and reflex swallowing elicited by continuous infusion of distilled water into the pharynx (2.5 ml/min) in 11 normal subjects. Ventilation was monitored using a pneumotachograph and swallowing was recorded by submental electromyogram. The CO2 ventilatory drive was increased by addition of external dead space, while ventilation, the frequency of swallows, and the timing of swallows in relation to the phases of the respiratory cycle were measured at steady-state conditions. We found that the CO2 ventilatory response is not influenced by continuous reflex swallowing but that hypercapnia influences the timing and frequency of these swallows. Signs of aspiration were never observed during continuous infusion of water at eucapnia, but seven of 11 subjects showed laryngeal irritation and/or pending aspiration during hypercapnia, and the incidence of laryngeal irritation was higher the greater the PCO2. Detailed analysis of laryngeal irritations consisting of single coughs in seven subjects revealed that the majority of laryngeal irritations occurred when swallows coincided with expiratory-inspiratory transition or when swallows coincided with inspiration, whereas laryngeal irritation after an expiratory swallow was never observed. These results suggest that the automatic respiratory control system is not influenced by continuous swallowing but that the coordination of swallowing and respiration may be compromised during hypercapnia.