BACKGROUND Exercise capacity in chronic obstructive pulmonary disease (COPD) is limited by both breathlessness and leg muscle fatigue. Neural respiratory drive, measured as diaphragm electromyogram (EMGdi) activity expressed as a proportion of maximum (EMGdi%max), quantifies the mechanical load on the respiratory muscles and relates closely to breathlessness. We tested the hypothesis that end-exercise EMGdi%max would be higher in patients stopping because of breathlessness than in those limited by leg fatigue. METHODS EMGdi, ventilation, rate of oxygen consumption (VO2), and ventilatory reserve (ventilation/maximum ventilatory volume ratio [VE/MVV]) were measured continuously in patients with COPD during exhaustive cycle ergometry. EMGdi was measured with a multipair oesophageal catheter passed per-nasally. Differences in physiological variables between groups of patients stopping because of breathlessness, leg fatigue, or both were assessed with one-way ANOVA. RESULTS 23 patients were included (median FEV1, 39% of predicted, IQR 30·0-56·8). End-exercise EMGdi%max was significantly higher in patients stopping exercise because of breathlessness (n=12, median EMGdi%max 75·7% [IQR 69·5-77·1]) than in those stopping because of leg fatigue (n=8, 44·1 [39·4-63·3]) or both (n=3, 74·1 [63·6-81·2]) (p=0·02). There were no significant differences between the groups in end-exercise ventilation (breathlessness 25·7 L/min [16·3-32·0] vs leg fatigue 31·5 [20·9-39·6] vs both 22·0 [17·7-35·7]), VO2, (13·4 mL/min per kg [11·6-14·2] vs 12·1 [10·4-14·8] vs 9·4 [9·1-12·4]), or VE/MVV (80·4% [72·6-88·3] vs 57·8 [52·1-92·6] vs 63·9 [34·5-88·9]). CONCLUSIONS These results suggest that patients limited by breathlessness due to ventilatory constraints can be identified as those reaching near-maximum levels of neural respiratory drive during exercise. Measurement of EMGdi%max during exercise could prove useful in identifying patients whose functional performance would be best optimised by improvment in pulmonary mechanics rather than interventions to train peripheral muscle groups. BACKGROUND None.