Impaired pulmonary mechanics or depression of the respiratory centers can limit the ventilatory response to inhaled carbon dioxide in patients with chronic obstructive pulmonary disease (COPD). We devised a method able to detect depressed neurogenic and chemical ventilatory drive during expiratory airflow obstruction. In 14 normal subjects, we impeded expiratory airflow while measuring the resultant decline in maximum voluntary ventilation (MVV) and the ventilatory response to rebreathing 7 percent CO2 (delta V/delta PCO2). The MVV and delta V/delta PCO2 fell proportionately and were closely correlated (r = 0.88). The lower limit for delta V/delta PCO2 during airway obstruction equalled 1.2 L/min/mm Hg X (observed MVV divided by predicted MVV). Nine patients with COPD and normal arterial carbon dioxide tension (PaCO2) all had normal values for delta V/delta PCO2 corrected for MVV; however, nine of 12 patients with COPD and elevated PaCO2 and bicarbonate levels had depressed values for delta V/delta PCO2. These data indicate that neurogenic and chemical depression to ventilation can be detected in patients with mechanical obstruction to expiratory airflow if delta V/delta PCO2 is corrected for changes in MVV.