['The ventilatory response to hypercapnia is greater breathing orally than nasally.', 'We hypothesize that this is due to higher nasal resistance to airflow compared with oral resistance. Seven normal male subjects were studied during both progressive hyperoxic hypercapnia (HC) and exercise (EX) until ventilation exceeded 40 L/min. Under each condition, subjects breathed via the nose only or the mouth only. For each breathing route, ventilation and pathway resistance were calculated simultaneously at the highest common exercise workload (140 +/- 20 watt; mean +/- SE) or the same end-tidal CO2 level (8.0 +/- 0.5%).', 'The ventilatory response breathing nasally was decreased by a similar amount for both EX and HC when compared with the oral route. The difference between nasal and oral ventilation was highly correlated with the difference between nasal resistance and oral resistance for both EX and HC (linear regression analysis; r = 0.91 for EX and r = 0.86 for HC; both P < 0.01).'] Is the breathing route dependence of ventilatory responses to hypercapnia and exercise modulated by upper airway resistance?