The purpose of this project was to better define factors that influence the resting PaCO2 and the change in the PaCO2 from rest to exercise in patients with moderate to severe chronic airflow obstruction. Pulmonary function testing, symptom-limited exercise tests using arterial catheter lines, and resting ventilatory and mouth occlusion pressure responses to hypercapnia and hypoxia were obtained in 19 patients (mean FEV1 = 1.07 +/- .50 L). The resting PaCO2 was closely related to the resting hypercapnic response. The highest correlation coefficient was between the PaCO2 and the ventilation at PCO2 = 60 obtained from the resting hypercapnic response (r = -0.74, p less than 0.001). A higher PaCO2 also tended to occur in patients with a lower FEV1 and a lower PaO2. The resting PaCO2 was not correlated significantly with the VT or the VD/VT. The change in the PaCO2 from rest to exercise was not significantly related to any measure of resting hypercapnic or hypoxic response, but rather was most dependent on the ventilatory response to exercise (delta VE/delta VCO2). Patients with a lower FEV1 or smaller decreases in the PaO2 with exercise tended to have larger increases in PaCO2 with exercise. The delta VE/delta VCO2 was higher in those with a high FEV1, a low resting PaCO2, and a low resting SaO2.