Recent studies have indicated that obesity is associated with hypertension, sodium retention, and increased sympathetic nervous system activity. The purpose of this study was to determine the role of renal nerves in mediating the sodium retention and hypertension associated with obesity. We determined the hemodynamic and renal excretory responses to a high-fat diet in control (n=6) and bilaterally renal-denervated (n=7) chronically instrumented dogs. After a control period of 8 days, dogs were placed on a high-fat diet for 5 weeks. In response to a high-fat diet, body weight increased from 19.9±2.2 to 29.9±2.4 kg in the control group and from 21.1±2.0 to 32.4±1.9 kg in the bilaterally renal-denervated group. Heart rate increased from 81±8 to 113±7 beats per minute in the control group and from 79±7 to 103±8 beats per minute in the bilaterally renal-denervated group. Arterial pressure increased significantly from 95±2 to 109±4 mm Hg in the control group. In contrast, 5 weeks of a high-fat diet in the bilaterally renal-denervated group did not significantly increase arterial pressure (which went from 87±3 to 90±4 mm Hg). Furthermore, the decrease in sodium excretion in response to the high-fat diet was significantly greater in the control group than in the bilaterally renal-denervated group. After 5 weeks of a high-fat diet, cumulative sodium retention was 455±85 mmol in the control group and only 252±47 mmol in the bilaterally renal-denervated group. Similar increases in glomerular filtration rate and renal plasma flow occurred in both groups in response to the high-fat diet. The results of this study indicate that the renal nerves play an important role in mediating the sodium retention and hypertension associated with obesity in dogs.