A transient relationship between change in cardiac output (CO) and ventilation and a steady-state relationship between VCO2 and ventilation has been documented. We sought to evaluate the steady-state relationship between CO, and minute ventilation (VE) after positional change and after vasodilator administration in 24 patients with chronic obstructive pulmonary disease (COPD) and mild pulmonary hypertension. Cardiac output was 25% higher (p = 0.003) and VE was 25% lower (p = 0.0001) in the supine position. The change in VE showed a strong correlation with the change in VCO2 (r = 0.693; p = 0.0004), but not with the change in CO. Twelve patients received hydralazine 200 mg orally over 24 h, and 12 patients received nifedipine as a single 10-mg oral dose. Cardiac output increased from 5.05 +/- 1.25 L/min to 6.91 +/- 2.07 L/min (p = 0.008) after hydralazine and increased from 4.34 +/- 1.47 L/min to 5.85 +/- 2.15 L/min (p = 0.001) after nifedipine. Minute ventilation increased from 14.8 +/- 3.0 L/min to 17.3 +/- 4.4 L/min (p = 0.008) after hydralazine, but did not change after nifedipine. The change in VE showed a strong correlation with the change in VCO2 after hydralazine (r = 0.889; p = 0.0004) and after nifedipine (r = 0.756; p = 0.005), but did not correlate with the change in CO. These data demonstrate that the change in VE that accompanies positional change or vasodilator administration in patients with COPD is strongly correlated with the change in VCO2 but not with the change in CO when measured under steady-state conditions.