Relation of threshold for perception of added inspiratory flow resistance to ventilatory and occlusion pressure response to hypercapnia during external flow-resistive loading was examined in 8 healthy volunteers and 14 patients with chronic obstructive pulmonary disease. Occlusion pressure response to hypercapnia without the load and the threshold for perception were similar between normal subjects and patients. Occlusion pressure at end-tidal PCO2 of 60 mm Hg increased to 134 +/- (SD) 23.4% (p less than 0.01) in normal subjects, but it did not change in patients (113.7 +/- 25.3%). Occlusion pressure response to hypercapnia increased to 155.4 +/- 60% (p less than 0.05) during ventilatory loading in normal subjects but it did not change in patients (105.9 +/- 33%). Inverse correlation between threshold values and changes after loading in occlusion pressure response to hypercapnia was seen in patients as well as in normal subjects. These results indicate in both normal subjects and patients with chronic obstructive pulmonary disease that occlusion pressure response to hypercapnia during the ventilatory loading includes signals from the higher central nervous system and that the lower the threshold, the higher the respiratory drive during the loaded ventilation.