Objectives: To define the clinical and polysomnographic features of a distinct variant of obstructive sleep-disordered breathing that is remarkably mild during rapid eye movement (REM) sleep. Design: Observational study and evaluation of polysomnographic and clinical records. Setting: American Academy of Sleep Medicine-accredited multidisciplinary sleep disorders center and laboratory. Patients: 35 medication-free subjects with clinical and polysomnographic severe obstructive sleep-disordered breathing selected for dominance of 1 of 2 disordered breathing patterns. Interventions: Positive airway pressure titration. Measurements and Results: Nasal pressure was used to score respiratory events. Sleep was scored by both the standard criteria and cyclic alternating pattern (CAP), and the distribution of respiratory events was tabulated and analyzed. A distinct clinical and polysomnographic syndrome emerged, CAP-dominant sleep-disordered breathing, characterized by severe relatively short cycle obstructive events during non-REM sleep that were mild in REM sleep. Characteristics include lower body mass index, fewer apneas, and a lower hypoxic burden as reflected by frequency and severity of nocturnal oxygen saturation. During positive pressure titration, a remarkable respiratory instability emerged selectively during CAP, in contrast to stability during REM sleep. This partial treatment failure was associated with persistent clinical symptoms. Conclusions: This variant of sleep apnea may reflect a dominant component of respiratory instability and periodic breathing coupled with upper-airway obstruction. Its existence questions the conventional practice of calculating global respiratory indexes. Besides positive airway pressure, measures to treat periodic breathing may be required.