Chemoreflex stimulation elicits both hyperventilation and sympathetic activation, each of which may have different influences on oscillatory characteristics of cardiovascular variability. We examined the influence of hyperventilation on the interactions between changes in R-R interval (RR) and muscle sympathetic nerve activity (MSNA) and changes in neurocirculatory variability, in 14 healthy subjects. We performed spectral analysis of RR and MSNA variability during each of the following interventions: 1) controlled breathing, 2) maximal end-expiratory apnea, 3) isocapnic voluntary hyperventilation, and 4) hypercapnia-induced hyperventilation. MSNA increased from 100% during controlled breathing to 170 +/- 25% during apnea (P = 0.02). RR was unchanged, but normalized low-frequency (LF) variability of both RR and MSNA increased markedly (P < 0.001). During isocapnic hyperventilation, minute ventilation increased to 20.2 +/- 1.4 l/min (P < 0.0001). During hypercapnic hyperventilation, minute ventilation also increased (to 19.7 +/- 1.7 l/min) as did end-tidal CO(2) (both P < 0.0001). MSNA remained unchanged during isocapnic hyperventilation (104 +/- 7%) but increased to 241 +/- 49% during hypercapnic hyperventilation (P < 0.01). RR decreased during both isocapnic and hypercapnic hyperventilation (P < 0.05). However, normalized LF variability of RR and of MSNA decreased (P < 0.05) during both isocapnic and hypercapnic hyperventilation, despite the tachycardia and heightened sympathetic nerve traffic. In conclusion, marked respiratory oscillations in autonomic drive induced by hyperventilation may induce dissociation between RR, MSNA, and neurocirculatory variability, perhaps by suppressing central genesis and/or inhibiting transmission of LF cardiovascular rhythms.