Ventilatory responses to inhaled CO₂ were measured during continuous negative pressure breathing (CNPB) in awake dogs. End expiratory lung volume (EELV) decreased linearly with pressure level during CNPB (correlation coefficient= 0.81, p<0.005) during air breathing. When CNPB was applied during 5% CO₂ inhalation, the decrease in EELV was not significantly different (p<0.5) from that during air breathing. As a result of a lowered EELV, tidal volume (V_T) significantly decreased by 22% and breathing frequency (f_B) increased by 68% in the steady state during air breathing (p<0.0001). These responses were similar during 5% CO₂ inhalation, thus the CO₂ response curve measured during CNPB shifted upward without a change in sensitivity (p>0.05). These results indicate additive effects of CNPB and CO₂ inhalation. The degree of hyperventilation during CNPB at eupnea was estimated to be 63% of that during control ventilation and was significantly greater than zero (p<0.0001), which suggests an alveolar hyperventilation due to CNPB. These results suggest that the mechanical alterations associated with n decrease in lung volume could play an important role in ventilatory control independently of chemical regulation of breathing. Thus, exercise hyperpnea, which is associated with a lowered functional residual capacity (FRC), may in part be explained by this mechanical stimulation of breathing.