Profound periodic sleep hypoxemia (as low as 9-10% saturation) was observed in 41 morbidly obese patients with obstructive sleep apnea (OSA). Group 1 consisted of 14 patients with awake hypercapnia (mean PaCO2 54 +/- 8 torr, s.d.) and group 2 were 27 with eucapnia (PaCO2 38.6 +/- 2.9). Group 1 OSA patients were more obese (BMI 48.7 +/- 8.5 vs 38.3 +/- 6.8 kg/m2, had lower FEV1 (61 +/- 17% vs 86 +/- 15% pred.) and lower FVC (62 +/- 16% vs 77 +/- 13% pred.), all the differences insufficient per se to account for hypercapnia. Group I remained apneic longer in REM (100 +/- 50 s vs 65 +/- 32 s), and tolerated lower mean SpO2 (pulse oximeter SaO2) in NREM (71 +/- 16% vs 81 +/- 7%) and lower minimum SpO2 values in NREM (54 +/- 12% vs 69 +/- 11%) (all the differences were significant, p < 0.05). We conclude that daytime hypercapnia predicts more severe sleep desaturation in NREM in obese patients with OSA. The combination of morbid obesity and hypercapnia with OSA is associated with the most profound and repeated hypoxemia ever reported as occurring without evident brain damage or death.