BACKGROUND Sympathoexcitation and respiratory instability are closely related to worsening of chronic heart failure. To elucidate the dynamic nature of respiratory modulation of sympathetic activity in patients with heart failure, we studied within-breath variation of muscle sympathetic nerve activity (MSNA) under various ventilatory volumes. RESULTS MSNA, blood pressure, and respiratory flow were recorded in 23 patients with left ventricular ejection fraction </=45%. Within-breath suppression of MSNA (neural silence) was found in 11 patients (MSNA bursts: 71+/-10/100 heartbeats) but not in the remaining 12 patients (MSNA bursts: 88+/-8/100 heartbeats). Patients without neural silence had a smaller tidal volume (391+/-70 versus 267+/-75 mL/m(2), P<0.01) and a higher respiratory rate (15+/-2 versus 19+/-4 breaths/min, P<0.01) during spontaneous respiration than those with neural silence. The relationship between tidal volume and minimal amplitude of MSNA bursts in each breath was obtained during random-interval breathing and fitted by an exponential function. The curve of patients without neural silence was shifted to the right and upward, which suggests that a greater tidal volume was required to suppress MSNA (227+/-70 versus 437+/-195 mL/m(2), P<0.01). CONCLUSIONS Sympathoexcitation in patients with chronic heart failure is closely related to both a decrease in resting tidal volume and an attenuated sympathoinhibitory effect of lung inflation reflex.