The influence of thiopental anesthesia on renal tubular sodium reabsorption was investigated in the well-trained dog. After administration of the anesthetic, renal sodium reabsorption was depressed, leading to the enhanced excretion of sodium and water. Associated with this response was a decrease in the plasma levels of epinephrine and norepinephrine. Neither renal hemodynamic functions nor the humoral factors, prostaglandin E, plasma renin activity, or arginine vasopressin appeared to be the major determinants of the natriuresis. These observations suggest that the administration of thiopental depresses renal sympathetic nerve activity, thereby diminishing the renal tubular transport of sodium.