A case of hyponatremia and then hypernatremia in a hospitalized patient receiving total parenteral nutrition (TPN) is described, and the etiologies, diagnoses, and treatments of hyponatremia and hypernatremia are reviewed. A 23-year-old man whose left leg had been amputated after a motorcycle accident required parenteral nutrition because of an ileus. After developing sepsis, he was given antimicrobials administered in standard dilutions of 5% dextrose injection, contributing 3 L of free water a day to his fluid intake. The patient subsequently became hyponatremic, and the sodium content of the TPN solution was increased to 140 meq/L. Multiple doses of furosemide and albumin were administered because of weight gain and edema of the lower extremity. After 14 days, all antimicrobial therapy was discontinued, and 2 days later the patient became hypernatremic. The sodium content of the TPN solution was decreased and then eliminated. Because of a 16-kg weight loss, diuretic therapy was stopped. This patient's hyponatremia was caused by administration of large amounts of sodium-free fluids (i.e., antimicrobials in 5% dextrose injection). The most appropriate management would have been to change the fluids in which the antimicrobials were diluted, with no change in the sodium content of the TPN solution. The patient's subsequent hypernatremia is best explained by a loss of free water. To manage this condition, it would have been appropriate to administer 5% dextrose injection to replace the free-water loss. Once the patient had reached baseline weight and therapy with the diuretic had been discontinued, maintenance therapy with 0.45% sodium chloride injection would have been beneficial. No change in the TPN sodium content should have been required. It is important to recognize all factors that predispose patients receiving TPN to hyponatremia and hypernatremia. Although the focus is often on the sodium content of the TPN solution, sodium and fluid can be administered by other means, including medication admixtures and maintenance intravenous fluids.