We tried to verify, in a clinical setting, the hypothesis that enhanced perception of dyspnoea (PD) and increased respiratory drive (RD): 1) relate to each other; and 2) elicit an integrated response that leads to a decrease in RD and tidal volume (VT) aimed at minimizing PD. In 34 patients with chronic obstructive pulmonary disease (COPD), dyspnoea was graded on a four-point scale after a Medical Research Council (MRC) questionnaire concerning respiratory symptoms. Patients were divided into four groups according to the dyspnoea score. Pulmonary volumes, arterial blood gases, VT, respiratory frequency (fR), inspiratory time (tI), expiratory time (tE), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) were measured. RD was also assessed in terms both of mouth occlusion pressure (P0.1) and electromyographic (EMG) activity of the respiratory muscles. Increase in dyspnoea rating was associated with decrease in vital capacity (VC), forced expiratory volume in one second (FEV1), MIP, VT and tI; and increase in arterial carbon dioxide tension (Pa,CO2), P0.1, and EMG (analysis of variance (ANOVA) and Bonferroni's test). A rapid and shallow pattern of breathing (RSB) characterized the group with the highest dyspnoea rating. Stepwise multiple regression analysis showed that: 1) tI and FEV1 accounted for a substantial proportion of the variability in VT and tI, respectively; 2) VT and MIP, together, predicted a substantial proportion of the variability in Pa,CO2 (r2 = 0.50). We conclude that, in patients with chronic obstructive pulmonary disease clinical rating of dyspnoea appears to be associated with muscle weakness and increase in respiratory drive. The increased respiratory drive is modulated into a rapid and shallow pattern of breathing, which leads to hypercapnia.