The main objective of the present study was to quantify the increase in tonic inspiratory activity (delta TIA) in response to continuous negative airway pressure (CNAP) in humans. TIA represents the activity in inspiratory muscles at the end of expiration. In 20 subjects, electromyograms (EMGs) were recorded from the diaphragm and parasternal intercostal muscles (ICM) with surface electrodes during control and at three different levels of CNAP (-0.3, -0.6, and -0.9 kPa; 1 kPa approximately 10 cmH2O). From these recordings we determined delta TIA and the amplitudes of phasic EMG activities (EMGphas) during CNAP and control. To evaluate the effects of CNAP on functional residual capacity (FRC), respiratory frequency, tidal volume, and minute ventilation, the subjects were connected to a closed breathing circuit. When the pressure at the airway opening was -0.9 kPa, mean values of delta TIA were 53 and 49% of control EMGphas for the diaphragm and ICM, respectively. In addition, EMGphas at airway opening pressure of -0.9 kPa had increased to 195 and 162% of control EMGphas for the diaphragm and ICM, respectively. The concomitant decrease in FRC was on average 18.7% of predicted FRC. Minute ventilation had increased significantly (P < 0.05) at all levels of CNAP compared with control. We conclude that CNAP is a forceful stimulus to increase TIA in humans in both the diaphragm and the ICM.