A 58-yr-old man with primary alveolar hypoventilation, central sleep apnea, and secondary polycythemia failed to improve when treated with respiratory stimulant medications, including oxtriphylline, acetazolamide, and medroxyprogesterone. In contrast, after institution of treatment with low-flow nocturnal oxygen, there was a marked decrease in the number and duration of sleep apneas, and an increase in the level of ventilation during sleep. These changes were sustained during 5 months of nocturnal oxygen therapy. The improvement produced by oxygen may have been due to the fact that the patient had no demonstrable ventilatory response to hypoxia during wakefulness, and therefore may have developed hypoxic brainstem depression during sleep. The findings suggest that oxygen therapy during sleep may be beneficial in patients with primary alveolar hypoventilation and central sleep apnea who demonstrate no ventilatory response to hypoxia during wakefulness.