We determined the relationship between mouth occlusion pressure and diaphragmatic electromyography during CO2 rebreathing with and without inspiratory flow resistance. Diaphragmatic electromyography was measured as a moving time average; occlusion pressures were measured 150 msec after onset of an inspiratory effort against a closed airway (P.15). P.15 versus diaphragmatic electromyographic plots during CO2 rebreathing with and without inspiratory flow resistance were linear. In 3 subjects the slope of P.15 versus diaphragmatic electromyography was unchanged with inspiratory flow resistance whereas in 3 others the slope increased, indicating greater inspiratory force for a given degree of diaphragmatic activity. We concluded that under unloaded conditions P.15 is a reliable index of respiratory neural output but may no longer reflect only inspiratory motoneuron drive during mechanical loading.