A 75-year-old woman with a history of stage IV metastatic melanoma underwent treatment with the CTLA-4 blocking agent Ipilimumab. She presented 2 months after initiating treatment with a severe headache. Laboratories were consistent with severe hyponatremia. MRI of the brain revealed enlargement of the pituitary gland, enhancement of the infundibulum, and an enhancing, centrally necrotic foci in the anterior pituitary. Based on the clinical and radiographic findings, she was diagnosed with treatment-related syndrome of inappropriate antidiuretic hormone secretion (SIADH). Effective treatment consisted of fluid restriction, hyperosmolar therapy, and steroids.