Patients with chronic obstructive pulmonary disease (COPD) often report an increase in breathlessness when they breathe through a mouthpiece. We hypothesized that stimulation of receptors in the oral mucosa modulates the sensation of breathlessness. We studied 10 normal naive volunteers in whom breathlessness was induced by having them breathe for 4 min with an inspiratory resistive load (18 cm H2O/L/s) while breathing was stimulated by CO2 inhalation (end-tidal PCO2 maintained at 55 mm Hg). Initially, subjects breathed with a tight-fitting face mask and inspiratory flow was displayed on a storage oscilloscope. In subsequent trials, the subjects were asked to match this trace, which controlled ventilation and the pattern of breathing. Subjects performed eight trials, four with the tight-fitting mask only (M) and four with a mouthpiece and the mask (MM). M and MM were alternated; the initial condition was chosen at random. Following each of the trials, subjects rated the intensity of their breathlessness by choosing a number from a modified Borg scale. On the average, subjects were more breathless while breathing with the mask and mouthpiece than with the mask alone (mean ratings of breathlessness 6.6 +/- 1.1 and 5.6 +/- 1.8 units, p less than 0.01). Six subjects repeated the protocol on 2 additional days: 1 day with inhalation of warm (34 degrees C), humidified air and 1 day after topical application of 4% lidocaine to the oral mucosa. Both these interventions abolished the differences in breathlessness between mask and mouthpiece and mask alone. We conclude that afferent information from oral mucosal stimulation influences the intensity of breathlessness.