We assessed the effects of chronic nasal continuous positive airway pressure (CPAP) therapy on lung function in a series of unselected patients with overlap syndrome, and we determined whether there were differences in the response induced by CPAP between hypercapnic (PaCO2 > or =45 mm Hg) and eucapnic patients with overlap syndrome. The study population included 55 unselected patients (48 men, mean age of 58.5 +/- 10.5 years) with a concurrent diagnosis of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea-hypopnea syndrome (OSAHS) who had been referred to the Department of Pulmonology of our hospital over 2 consecutive years and in whom work-up studies resulted in the prescription of nasal CPAP therapy. An apnea-hypopnea index (AHI) greater than or equal to 10 in the cardiorespiratory polygraphy was required for the diagnosis of OSAHS. A forced expiratory volume in one second (FEV1) less than 80% and FEV1-forced vital capacity (FVC) ratio less than 70% of the reference values were required for the diagnosis of COPD. Control lung function studies and arterial blood gas measurements were performed at 6 and 18 months of CPAP therapy. These patients with overlap syndrome accounted for 28.5% of all patients with OSAHS treated with CPAP during the study period. The mean AHI was 37.3 +/- 26.1 and the mean CPAP level 7.3 +/- 1.3 cm H2O. Thirty-three patients were hypercapnic (PaCO2 > or = 45 mm Hg) and 22 eucapnic. The hypercapnic group had higher AHI value (44.3 +/- 26.9) than the eucapnic group (28.6 +/- 21.9) (P < 0.05). After 6 months of CPAP therapy, there were statistically significant increases in PaO2, FEV1, and FVC, accompanied by significant decreases in PaCO2, serum bicarbonate levels, and alveolar-arterial oxygen difference. Response of overlap syndrome patients to CPAP therapy was superior in the hypercapnic group, particularly in relation to improvement of arterial blood gases. However, statistically significant differences in all parameters for the comparison between 6 and 18 months were not recorded.