Cheyne-Stokes respiration (CSR) is a form of periodic breathing associated with periodic oscillations in blood pressure (BP) and heart rate (HR), which have been attributed to hypoxia and arousals from sleep. We hypothesized that periodic alterations in ventilation alone would promote oscillations in BP and HR. Seven healthy, wakeful subjects breathed in three patterns, as follows: (1) regular breathing (RB); (2) periodic breathing with three (PB3: cycle frequency = 0.035 Hz) augmented breaths alternating with 20-s apneas; and (3) periodic breathing with five (PB5: cycle frequency = 0.030 Hz) augmented breaths alternating with 20-s apneas. SaO2 remained above 95% throughout. During periodic breathing, peaks in BP and HR occurred during the ventilatory period and troughs occurred during apnea. The magnitudes of systolic BP oscillations increased significantly from RB (14 +/- 5 mm Hg) to PB3 (20 +/- 4 mm Hg) and PB5 (25 +/- 7 mm Hg; p < 0.005). HR oscillations also increased from regular breathing (13 +/- 6.0 beats/min) to PB3 (20.2 +/- 2.3 beats/min) and PB5 (20.2 +/- 4.7 beats/ min; p < 0.01). Spectral analysis showed that during periodic breathing there were discrete peaks in the spectral power of ventilation, BP, and R-wave-to-R-wave interval at the periodic breathing cycle frequencies. We conclude that oscillations in ventilation occurring during periodic breathing can amplify and entrain oscillations in BP and HR in the absence of hypoxia or arousals from sleep.