tory sinus arrhythmia (RSA) is generally known as the autonomically mediated modulation of the sinus node pacemaker frequency in synchrony with respiration. Cardiorespiratory interactions have been largely investigated during sinus rhythm, whereas little is known about interactions during reentrant arrhythmias. In this study, cardiorespiratory interactions at the atrial and ventricular level were investigated during atrial flutter (AFL), a supraventricular arrhythmia based on a reentry, by using cross-spectral analysis and computer modeling. The coherence and phase between respiration and atrial (␥ AA 2 , AA) and ventricular (␥ RR 2 , RR) interval series were estimated in 20 patients with typical AFL (68.0 Ϯ 8.8 yr) and some degree of atrioventricular (AV) conduction block. In all patients, atrial intervals displayed oscillations strongly coupled and in phase with respiration (␥ AA 2 ϭ 0.97 Ϯ 0.05, AA ϭ 0.71 Ϯ 0.31 rad), corresponding to a paradoxical lengthening of intervals during inspiration. The modulation pattern was frequency independent, with in-phase oscillations and short time delays (0.40 Ϯ 0.15 s) for respiratory frequencies in the range 0.1-0.4 Hz. Ventricular patterns were affected by AV conduction type. In patients with fixed AV conduction, ventricular intervals displayed oscillations strongly coupled (␥ RR 2 ϭ 0.97 Ϯ 0.03) and in phase with respiration ( RR ϭ 1.08 Ϯ 0.80 rad). Differently, in patients with variable AV conduction, respiratory oscillations were secondary to Wencheback rhythmicity, resulting in a decreased level of coupling (␥ RR 2 ϭ 0.50 Ϯ 0.21). Simulations with a simplified model of AV conduction showed ventricular patterns to originate from the combination of a respiratory modulated atrial input with the functional properties of the AV node. The paradoxical frequency-independent modulation pattern of atrial interval, the short time delays, and the complexity of ventricular rhythm characterize respiratory arrhythmia during AFL and distinguish it from normal RSA. These peculiar features can be explained by assuming a direct mechanical action of respiration on AFL reentrant circuit. respiratory arrhythmia; heart rate variability; reentry; cross-spectral analysis; mechanoelectrical feedback THE FIRST REPORT ON AN INTERACTION between respiration and heart rate is ascribed to Ludwig and dates back as early as 1847 (34). The phenomenon, named respiratory sinus arrhythmia (RSA), was described as an acceleration of the heart rate during inspiration followed by a slowing during expiration. Since then, several studies have been performed that have revealed the complex nature of the interaction, characterized by frequency-dependent behaviors (1,4,13,21,55), and shed light on its origin. Several mechanisms have been proposed for the generation of RSA, including the direct interaction between central cardiorespiratory centers within the brain stem, pulmonary reflex pathways, respiratory gating of central arterial baroreceptor afferent input, an atrial reflex, and oscillations in arterial PCO 2...