Several sympatho-excitatory reflexes such as the cardiac sympathetic afferent reflex (CSAR) and arterial chemoreflex, are significantly augmented and contribute to elevated sympathetic outflow in chronic heart failure (CHF). This study was undertaken to investigate the interaction between the CSAR and the chemoreflex in CHF, and to further identify the involvement of angiotensin type 1 receptors (AT₁R) in the nucleus of the tractus solitarius (NTS) in this interaction. CHF was induced in rats by coronary ligation. Acute experiments were performed in anesthetized and vagotomized rats. The chemoreflex-induced increase in cardiovascular responses was significantly greater in CHF than in sham rats after either chemical or electrical activation of the CSAR. Inhibition of the CSAR by epicardial lidocaine reduced the chemoreflex-induced effects in CHF rats but not in sham rats. Bilateral NTS injection of the AT₁R antagonist losartan (10 and 100 pmol) dose-dependently decreased basal sympathetic nerve activity in CHF but not in sham rats. This procedure also abolished the CSAR-induced enhancement of the chemoreflex. The discharge and chemosensitivity of NTS chemosensitive neurons were significantly increased following stimulation of the CSAR in sham and CHF rats, while CSAR inhibition by epicardial lidocaine significantly attenuated chemosensitivity of NTS neurons in CHF but not in sham rats. Finally, protein expression of AT₁R in the NTS was significantly higher in CHF than in sham rats. These results demonstrate that the enhanced cardiac sympathetic afferent input contributes to an excitatory effect of chemoreflex function in CHF, which is mediated by an NTS-AT₁R dependent mechanism.