Cheyne-Stokes respiration (CSR) is a form of periodic breathing associated with oscillations in heart rate (HR) and blood pressure (BP), which have previously been attributed to the effects of intermittent hypoxia and arousals from sleep. We herein review the major findings from a series of experiments, in which we explored the possibility that the ventilatory oscillations of CSR can independently modulate HR and BP. Using frequency spectral analysis, we showed that CSR in patients with heart failure causes oscillations in HR and BP that are eliminated by abolition of ventilatory oscillations, but persist during administration of supplemental O2 sufficient to prevent hypoxia. Analysis of the effects of arousals showed they have little or no effect on HR or BP independent of associated changes in ventilation. Finally, we showed that during simulated CSR, healthy awake patients were able to cause HR and BP oscillations in the absence of hypoxia or arousals. We conclude that ventilatory oscillations during Cheyne-Stokes respiration can modulate HR and BP independent of the effects of hypoxia and arousals from sleep.