Acute unilateral nephrectomy (AUN) increases electrolyte excretion by the remaining kidney and is associated with a decrease in cardiac output (CO). We studied anesthetized dogs to determine the role of the vagus nerves in these responses to AUN. In six intact animals, AUN increased sodium excretion (U Na V) from 31.7 ± 13.9 to 47.5 ± 14.3 /iEq/min (P < 0.05) and potassium excretion (U K V) from 29.3 ± 5.2 to 62.0 ± 11.4 /iEq/min (P < 0.02) as CO fell from 2.8 ± 0.2 to 1.9 to 0.3 liters/min (P < 0.005), and blood pressure and total peripheral resistance increased; no change in glomerular filtration rate (GFR) occurred, but renal blood flow fell significantly. In seven dogs undergoing sham nephrectomy, no signficant changes in any of these variables occurred. In 12 dogs with bilateral cervical vagotomy, AUN increased U N «V from 19.3 ± 5.3 to 39.6 ± 13.7 /lEq/min (P< 0.05) and U K V from 35.7 ± 5.5 to 46.8 ± 5.8 /iEq/min, (P < 0.001), without changes in GFR, renal blood flow, or mean arterial pressure. However, CO and total peripheral resistance did not change in this group. In nine dogs given intravenous atropine sulfate (0.067 mg/kg), AUN again resulted in comparable increases in cation excretion, but no significant change in CO occurred. These studies demonstrate that the increased electrolyte excretion seen after AUN is not prevented by bilateral cervical vagotomy or by atropine administration. However, the decrease in CO associated with AUN does not occur under these circumstances, indicating that reflex vagal efferent activity is responsible for this hemodynamic change. Therefore, the increase in electrolyte excretion after AUN can be dissociated from the decrease in CO.