The present study aimed to determine whether peripheral and/or central chemoreflex function is altered in chronic heart failure (CHF) and whether altered chemoreflex function contributes to sympathetic activation in CHF. A rabbit model of pacing-induced CHF was employed. The development of CHF (3-4 wk of pacing) was characterized by an enlarged heart, an attenuated contractility, and an elevated central venous pressure. Renal sympathetic nerve activity (RSNA) and minute volume (MV) of ventilation in response to stimulation of peripheral chemoreceptors by isocapnic/hypoxic gases were measured in the conscious state. It was found that the baseline RSNA at normoxia was higher in CHF rabbits than in sham rabbits (35. 00 +/- 4.03 vs. 20.75 +/- 2.87% of maximum, P < 0.05). Moreover, the magnitudes of changes in RSNA and MV in response to stimulation of the peripheral chemoreceptors and the slopes of RSNA-arterial PO2 and MV-arterial PO2 curves were greater in CHF than in sham rabbits. Inhibition of the peripheral chemoreceptors by inhalation of 100% O2 decreased RSNA in CHF but not in sham rabbits. The central chemoreflex function, as evaluated by the responses of RSNA and MV to hyperoxic/hypercapnic gases, was not different between sham and CHF rabbits. These data suggest that an enhancement of the peripheral chemoreflex occurs in the rabbit model of pacing-induced CHF and that the enhanced peripheral chemoreflex function contributes to the sympathetic activation in the CHF state.