We investigated a possible effect of doxapram (a respiratory stimulant) on the peripheral chemoreceptors in man (8 control subjects, 11 bronchitics, and 4 emphysematous). In addition, we determined whether infusion of doxapram could augment blunted chemosensitivity to hypoxia or hypercapnia seen in both chronic obstructive pulmonary disease (COPD) patients and normal subjects. Doxapram infusion caused a significant increase in delta VE/delta SaO2 (p less than 0.05), as well as delta Po.1/delta SaO2 (p less than 0.05) in control subjects, although the changes in both delta VE/delta PeAco2 (where, PeAco2 = end-tidal Pco2) and delta Po.1/delta PeAco2 did not attain significant level. Control subjects with low baseline delta Po.1/delta SaO2 showed significantly larger changes in both delta Po.1/delta SaO2 and delta VE/SaO2 during doxapram infusion than the patients with chronic bronchitis (0.02 less than p less than 0.05). We conclude that doxapram increases chemosensitivity to hypoxia and slightly increase chemosensitivity to hypercapnia, indicating its primary action being stimulation of peripheral chemoreceptors, and doxapram stimulates chemoreceptors little in patients with chronic bronchitis, whereas blunted hypoxic response in normal subjects could be increased markedly.