Described is a 67-year-old man whose initial symptoms evoked an obesity-hypoventilation syndrome. Polysomnography showed hypopneas associated with O2 desaturation episodes, and no apnea; maximal changes were noted during REM sleep. A few months later, in spite of marked weight loss, acute alveolar hypoventilation occurred and necessitated mechanical ventilatory support. Tracheostomy was performed. The patient appeared to be dependent on nocturnal ventilatory assistance. Diaphragmatic paralysis was noted in addition to clinical and electrodiagnostic evidence of amyotrophic lateral sclerosis. While the patient was not ventilated, a nocturnal recording of SaO2 again revealed desaturation episodes partly corrected by O2 2 L/min administered through the tracheostomy tube. With volume-controlled ventilation, desaturations completely disappeared, although no oxygen enrichment of the air was provided. We speculate that sleep disorders with hypopneas and O2 desaturation episodes were the initial symptoms of amyotrophic lateral sclerosis. This leads us to suggest that nonspecific respiratory muscle fatigue frequently seen in COPD might be included in the hypothetic causes of nocturnal hypoxemia.