Factors responsible for very low frequency oscillations (VLF; cycle > 30 s) in the cardiovascular system remain obscure. We tested the hypothesis that increased peripheral chemosensitivity is important in the pathogenesis of VLF oscillations in patients with chronic heart failure (CHF). Fourteen male patients with stable, moderate to severe CHF (age 60 +/- 1.1 yr, ejection fraction 23 +/- 11%) and reproducible VLF oscillations in heart rate underwent a protocol consisting of three consecutive 20-min phases during which they breathed air, hyperoxia (O2 via mask, 60% O2 concn), and air again. Autoregressive spectral analysis of R-R intervals, blood pressure, and respiration was used to quantify total oscillatory power (TP), VLF, low (0.04-0.15 Hz)- and high (0.15-0.40Hz)-frequency power, and the coherence between these signals. Peripheral chemosensitivity was studied by assessing the ventilatory response to hypoxia using transient inhalations of pure N2. Discrete VLF rhythms were seen in R-R intervals in all 14 patients, in blood pressure in 7 of 14, and in respiration in 8 of 14 patients. A significant coherence (> 0.5) between heart rate and systolic blood pressure within the VLF band with mean phase value of -140 degrees, suggesting an antibaroreflex relationship, was seen in six subjects. Transient hyperoxia abolished the VLF oscillations in most subjects (12 of 14 in R-R intervals) and decreased R-R variability power within the VLF band. This response significantly correlated with peripheral chemoreceptor sensitivity (r = 0.77, P = 0.014). This study suggests that in CHF, enhanced peripheral chemoreceptor activity may facilitate slow oscillations in the cardiorespiratory signals.