The effect of transtracheal oxygen administration by means of a 9-French (2.7 mm) percutaneous catheter was assessed in five patients with severe obstructive sleep apnea. We hypothesized that the delivery of oxygen below the site of airway obstruction should reduce the arterial oxygen desaturation during apneas and hypopneas, thereby increasing respiratory stability. Standard sleep and respiratory measurements were recorded in these subjects with all-night polysomnography on nonconsecutive nights during four experimental conditions: room air (BL), nasal continuous positive airway pressure (CPAP), nasal O2 (NC O2), and transtracheal O2 (TT O2). In three of these subjects, room air was infused (TT RA) at flow rates comparable to TT O2. Compared with baseline room air measurements, TT O2 not only significantly increased the SaO2 nadir from 70.4 percent to 89.7 percent (p less than 0.01), but it also reduced the frequency of sleep apnea/hypopnea from 64.6 to 26.2/h sleep (p less than 0.01). NC O2 ameliorated desaturation during apnea/hypopnea (mean SaO2 nadir, 86.2 percent; p less than .01) but did not significantly alter frequency (59.0/h sleep). Nasal CPAP was the most effective means of reducing sleep apnea/hypopnea (13.8/h sleep) but did not abolish desaturations when apneas occurred (mean SaO2 nadir, 80.0 percent). Compared with oxygen, transtracheal infusion of room air appeared to be somewhat effective; however, the small number of studies with TT RA precluded statistical analysis. We believe that TT O2 is superior to NC O2 for some patients with obstructive sleep apnea because continuous oxygen flow below the site of airway obstruction more reliably prevents alveolar hypoxia and respiration is stabilized. Infusion of air or oxygen through the tracheal catheter flow may also increase mean airway pressure and reduce obstructive apnea similar to nasal CPAP. We conclude that TT O2 may be an effective alternative mode of therapy for some patients with severe sleep apnea/hypopnea when nasal CPAP is not tolerated or when combined oxygen and nasal CPAP are required.