Our patient is a 44-year-old male who was brought in by ambulance for altered mental status. As per the patient's wife, the week prior to admission he began staring off in space and responding to internal stimuli. His mentation deteriorated, and he began hallucinating and became aggressive, at which point she brought him to the emergency department. Six months prior to admission, he was diagnosed with metastatic renal cell carcinoma and underwent primary cancer removal with subsequent right nephrectomy. He was found to have multiple leiomyomas and was referred to the National Cancer Institute in Maryland. Genetic testing showed autosomal dominant Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC). Follow-up L-spine MRI for back pain showed extensive metastasis to the lumbar spine, sacrum, and right and left ilium. He was started on targeted immunotherapy of nivolumab and given a single dose of 240 mg two weeks prior to admission. On presentation, he was febrile and unable to communicate. He was acutely encephalopathic and responding to internal stimuli. During the interview, he was experiencing and responding to auditory, visual, and tactile hallucinations. On admission, his blood pressure was 122/86 with a pulse of 118 and temperature of 100.8 F. Chest X-ray showed no signs of pneumonia or metastases. Brain MRI showed no evidence of metastases or lymphoreticular disorder. Blood work showed an elevated white blood cell count of 16.61, unchanged from a previous admission due to home medication of Decadron. Serum Na was 132 with AST/ALT 36/72, TBili 0.5, alkaline phosphatase 246, and a creatinine of 2.0 at his baseline. Urinalysis performed in the ED showed packed hyaline casts without superimposed urinary tract infection. Blood cultures were drawn, and he was started on normal saline and oxygen. His home medications included methadone, naproxen, omeprazole, oxycodone, risperidone, hydromorphone, trazodone, benzonate, dexamethasone, buproprion, cyclobenzaprine, and ondansetron. Given the nature of the patient's pain and the severity of his illness, all of his home medications were continued. He was started on Haldol for agitation and transferred to the medical intensive care unit for treatment of encephalopathy. On examination, he exhibited garbled speech and continued encephalopathy. Initial attempts to sedate the patient using ketamine were effective and resulted in increased lucidity. He eventually became hypertensive and required treatment with Precedex while in the MICU. After 5 days in the MICU, the patient was found to be speaking in short sentences and was alert, awake, and oriented to person, place, and time with no signs of encephalopathy. Blood cultures throughout the stay showed no growth. Given the patient's lack of metabolic abnormalities, acute infection, continuation of all home medication throughout the hospital stay, and temporal resolution of symptoms after removal of nivolumab, he was diagnosed with nivolumab-induced encephalitis. The patient was discharged home on his home medications and scheduled for outpatient radiation therapy with discontinuation of nivolumab. After a short stay at home, patient was advanced to hospice and soon after passed away from metastatic renal cell carcinoma.