Object: In this paper, the authors' goal was to describe the occurrence of alternating hypernatremia and hyponatremia in pediatric patients who underwent resection of hypothalamic hamartomas (HHs) for epilepsy. Hypernatremia in patients after pituitary or hypothalamic surgery can be caused by diabetes insipidus (DI), whereas hyponatremia can occur due to a syndrome of inappropriate antidiuretic hormone, cerebral salt wasting, or excessive administration of desmopressin (DDAVP). The triphasic response after surgery in the pituitary region can also explain variations in sodium parameters in such cases. Methods: One hundred fifty-three patients with HH who underwent surgery were enrolled in a prospective study to monitor outcomes. Of these, 4 patients (2.6%) were noted to experience dramatic alterations in serum sodium values. The medical records of these patients were identified and evaluated. Results: Patients' ages at surgery ranged from 1.2 to 6.0 years. All patients were girls. Two patients had Delalande Type IV lesions (of 16 total Type IV lesions surgically treated) and 2 had Type III lesions (of 39 total Type III lesions). All patients had a history of gelastic seizures refractory to medication. Seizure frequency ranged from 3 to 300 per day. After surgery, all patients experienced hypernatremia and hyponatremia. The largest fluctuation in serum sodium concentration during hospitalization in a single patient was 53 mEq/L (range 123-176 mEq/L). The mean absolute difference in maximum and minimum sodium values was 38.2 mEq/L. All patients exhibited an initial period of immediate DI (independent of treatment) after surgery followed by a period of hyponatremia (independent of treatment), with a minimum value occurring between postoperative Days 5 and 8. All patients then returned to a hypernatremic state of DI, and 3 patients still require DDAVP for DI management. A second occurrence of hyponatremia lasting several days without DDAVP administration occurred in 2 patients during their hospitalization between periods of hypernatremia. One patient stabilized in the normal range of sodium values prior to discharge from rehabilitation without the need for further intervention. At last follow-up, 3 patients are seizure-free. Conclusions: Severe instability of sodium homeostasis with hypernatremia and hyponatremia is seen in up to 2.6% of children undergoing open resection of HH. This risk appears to be related to HH type, with a higher risk for Types III (2 [5.1%] of 39) and IV (2 [12.5%] of 16) lesions. Here, the authors describe alternating episodes of hypernatremia and hyponatremia in the postoperative period following HH surgery. Management of this entity requires careful serial assessment of volume status and urine concentration and will often require alternating salt replacement therapy with DDAVP administration.