Vibration of chest wall inspiratory muscles during inspiration (in-phase) reduces breathlessness associated with hypercapnia and resistive loading in normal subjects and in patients with chronic obstructive pulmonary disease (COPD) at rest. To evaluate further the effect of chest wall vibration on breathlessness ("breathing discomfort") in patients, we studied 10 subjects 52 to 79 yr of age with severe dyspnea (mean FEV1, 0.75 L, 27% predicted). On a single day, we used two separate stimuli to produce mild to moderate breathlessness (BR): Protocol 1, steady-state hypercapnia; Protocol 2, exercise with a lower extremity ergometer. During each protocol, we applied in-phase chest wall vibration (CW) randomly alternating with one of two controls: deltoid vibration (DV) or no vibration (NV). During hypercapnia, CW significantly reduced BR (DV, 2.9 +/- 2.1; CW, 2.3 +/- 1.4; p < 0.05; NV, 3.3 +/- 2.1; CW, 2.6 +/- 2.0; p < 0.01) without significant changes in ventilation. During exercise, CW did not significantly alter BR relative to controls. These findings may be explained by the effect of vibration on the sense of respiratory effort and/or by improvement of the match between efferent motor commands and afferent information from the respiratory system. The lack of effect during exercise on BR suggests there may be a "therapeutic window" or range of conditions within which CW is effective in reducing dyspnea in patients with COPD.