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INTRODUCTION There are many mechanisms for improving the clinical and blood gas status of patients with the obesity hypoventilation syndrome (OHS) or chronic obstructive pulmonary disease (COPD) by non-invasive ventilation (NIV) at home. Our objective was to set up a pilot study to evaluate the potential modification of the sensitivity of the respiratory centers to CO2 by NIV in paired new COPD and OHS patients. METHODS We assessed the sensitivity of the respiratory centers to CO2 by the Read method in 3 COPD patients and 3 OHS patients newly treated by NIV and again 3 months later. We compared their results to those of 6 control subjects. RESULTS All the patients included had altered ventilatory responses to CO2 with slopes of less of than 1 L.min-1.mmHg-1. Mean coefficients of variation were significantly higher in patients than in healthy subjects (P=0.007). Patients who improved their CO2 sensitivity slope were those most observant of NIV. CONCLUSION This work showed significant changes in the ventilatory response to hypercapnia in patients with either OHS or COPD after NIV therapy. The significance of these changes deserves to be studied.