Patients with severe COPD are frequently flow-limited during expiration at rest. When expiratory flow is at its maximum, application of negative pressure at the mouth should accentuate dynamic compression downstream from the flow-limiting segment (FLS) without substantially affecting flow or pressure upstream. The purpose of this study was to determine the ventilatory response to such intervention and to determine its effect on respiratory sensation. Such responses should reflect the effect of airway receptors downstream from the FLS. Nine patients with severe COPD (FEV1 +/- SE = 27 +/- 3% predicted) breathed into a closed-circuit apparatus that incorporated a rolling-seal spirometer. The spirometer was fitted with a linear actuator that caused mouth pressure to become negative in proportion to expiratory flow (expiratory assistance, EA). Ventilatory responses were measured during 4 min of EA (-9.7 cm H2O/L/s) and were compared with those during control periods (4 min each) before and after this (C1 and C2). Sense of breathing effort was assessed at 1-min intervals by asking the subject to point to a category scale of 1 to 5, with 1 being minimal effort and 5 indicating that breathing was very difficult. There were small but significant (p less than 0.05) decreases in TI (mean +/- SE, -0.2 +/- 0.05 s) and TE (-0.3 +/- 0.07 s), with increases in breathing frequency (+2.25 +/- 0.7) and ventilation (+1.5 +/- 0.6 L/min). No significant changes were observed in tidal volume or end-expiratory volume. The EA caused a highly significant (p less than 0.001) increase in the sense of breathing effort.(ABSTRACT TRUNCATED AT 250 WORDS)