We examined the clinical and respiratory physiologic characteristics of 18 patients in whom a diagnosis of central sleep apnea syndrome was established by overnight polysomnographic studies. The patients could be readily divided into 2 groups on the basis of physiologic and clinical criteria. Five patients had an awake arterial PCO2 (PaCO2) of 53 +/- 4 (SEM) mmHg in the absence of intrinsic bronchopulmonary disease, a ventilatory response to CO2 of 0.6 +/- 0.2 L/min/mmHg, and a hemoglobin concentration of 180 +/- 6 g/L. Their clinical course was dominated by recurrent episodes of respiratory failure. In contrast, the other 13 patients had an awake PaCO2 of 35 +/- 1 mmHg (p less than 0.001), a CO2 response of 2.9 +/- 0.4 L/min/mmHg (p less than 0.005), and a hemoglobin concentration of 150 +/- 5 g/L (p less than 0.005). Clinically, they presented with features typical of sleep apnea; none had a history of respiratory failure. Despite the clinical and physiologic differences between the 2 groups, there were no differences between them in the frequency or duration of nocturnal apneic events or in sleep architecture. The findings indicate that the central sleep apnea syndrome is not a homogeneous disease entity. Rather, it includes 2 groups of patients that are clinically and physiologically distinct, with 1 group chronically hypoventilating and the other group either chronically hyperventilating or ventilating normally.