Mouth occlusion pressure at 0.1 s (P0.1) and minute ventilation (VE) were measured at rest and during progressive hypercapnia in 32 patients. Under double-blind conditions and according to a 2 x 2 Latin-square design, half the patients received one oral dose of diazepam and its placebo. Using the same design, the other half received zopiclone and its placebo. Normocapnic and moderately hypoxemic patients between the ages of 21 and 69 with moderate to severe chronic obstructive pulmonary disease were included in the study. Diazepam produced a statistically significant decrease (p less than 0.05) over its placebo in delta P0.1/delta PETCO2 values following CO2 rebreathing. Zopiclone did not influence either delta P0.1/delta PETCO2 or delta VE/delta PETCO2, but produced a significant increase in respiratory frequency. However, no statistically significant differences were observed between the two active treatments.