Maximal inspiratory and transdiaphragmatic pressures vary with lung volume but the possibility that some of this variability reflects variable voluntary drive to the diaphragm has not been investigated systematically. We assessed the influence of lung volume on the ability to activate the diaphragm with voluntary effort during maximal Mueller manoeuvres. Voluntary activation of the diaphragm was assessed using twitch interpolation with bilateral phrenic nerve stimulation in 6 subjects. Each performed 10 maximal efforts at lung volumes around functional residual capacity (FRC) and additional efforts at volumes above and below FRC. Voluntary activation of the diaphragm was higher at lung volumes above FRC (> 60% TLC; activation 98.3 +/- 2.6%) than at lung volumes around FRC (45-60% TLC; activation 95.5 +/- 3.5%) and below FRC (< 45% TLC; activation 83.3 +/- 15.8%; p < 0.05). Submaximal diaphragm activation at low lung volumes may reflect differences in the length-tension relationships of the various inspiratory muscles and/or reflex inhibition of phrenic motoneurones at low lung volumes.