The aim of the present study was to use the diaphragm electromyogram (EMG(di)) to compare levels of neural respiratory drive (NRD) in a cohort of healthy subjects and chronic obstructive pulmonary disease (COPD) patients, and to investigate the relationship between NRD and pulmonary function in COPD. EMG(di) was recorded at rest and normalised to peak EMG(di) recorded during maximum inspiratory manoeuvres (EMG(di) % max) in 100 healthy subjects and 30 patients with COPD, using a multipair oesophageal electrode. EMG(di) was normalised to the amplitude of the diaphragm compound muscle action potential (CMAP(di,MS)) in 64 healthy subjects. The mean+/-sd EMG(di) % max was 9.0+/-3.4% in healthy subjects and 27.9+/-9.9% in COPD patients, and correlated with percentage predicted forced expiratory volume in one second, vital capacity and inspiratory capacity in patients. EMG(di) % max was higher in healthy subjects aged 51-80 yrs than in those aged 18-50 yrs (11.4+/-3.4 versus 8.2+/-2.9%, respectively). Observations in the healthy group were similar when peak EMG(di) or CMAP(di,MS) were used to normalise EMG(di). Levels of neural respiratory drive were higher in chronic obstructive pulmonary disease patients than healthy subjects, and related to disease severity. Diaphragm compound muscle action potential could be used to normalise diaphragm electromyogram if volitional inspiratory manoeuvres could not be performed, allowing translation of the technique to critically ill and ventilated patients.