Hypotension occurring during hemodialysis is often accompanied by paradoxical bradycardia. However, the mechanism is poorly understood. This study was designed to determine the role of the sympathetic nervous system in hemodialysis-induced hypotension and bradycardia. We measured efferent sympathetic nerve activities to the heart (CNA), kidney (RNA), liver (HNA), spleen (SpNA), and adrenal gland (AdNA), along with heart rate (HR), blood pressure (BP), central venous pressure (CVP), and left atrial pressure (LAP) during hemofiltration performed at a rate of 0.3 mL∙kg−1∙min−1 for 30 min in anesthetized dogs. The response to hemorrhage was also studied at the same bleeding speed. Hemorrhage caused a decrease in BP (−18 ± 1 mmHg; 1 mmHg = 133.3 Pa) with reflex increases in HR (7 ± 2 beats/min) and sympathetic nerve activities. In contrast, hemofiltration caused a decrease in CNA (85 ± 18%), HNA (86 ± 11%), and SpNA (88 ± 11%) with greater decreases in BP (−43 ± 10 mmHg) and HR (−27 ± 14 beats/min) than hemorrhage. During hemofiltration, the decreases in BP, HR, CNA, HNA, and SpNA were attenuated after vagotomy. Hematocrit increased by 6.5% at 30 min after hemofiltration, whereas it decreased by 4.3% after hemorrhage. These results suggest that hemofiltration suppresses the sympathetic nervous system, resulting in decreases in HR and BP. Furthermore, this sympathetic suppression during hemofiltration is mediated by vagal afferents.Key words: hemodialysis, baroreceptor reflex, sympathetic nerve activity, hemorrhage, vagus nerve.