The fluorinated pyrimidine 5-fluorouracil (5-FU) is an anticancer agent used in most adjuvant and palliative treatment regimens for colorectal cancer. Neurotoxicities are considered extremely rare side effects of 5-FU. Here, we report a case of 5-FU-induced encephalopathy, manifesting as seizures and delirium, in an era of oxaliplatin-containing chemotherapy. If ammonia levels are elevated, lactulose may be considered in the initial management of neuropsychiatric complications from 5-FU. KEY WORDSColorectal cancer, 5-fluorouracil, oxaliplatin, chemotherapy, complications CASE DESCRIPTIONA 53-year-old Korean man who had undergone curative surgical resection for stage III (T3N2M0) colon cancer was evaluated in clinic by his medical oncologist before the start of adjuvant chemotherapy. He appeared clinically well on assessment and proceeded to receive his first cycle of modified chemotherapy. This regimen consisted of oxaliplatin 85 mg/m 2 , folinic acid 400 mg/m 2 , and 5-fluorouracil (5-FU) 400 mg/m 2 bolus on day 1, followed by 5-FU 2400 mg/m 2 by continuous infusion over the next 46 hours. Dexamethasone 12 mg and ondansetron 8 mg were given as pre-medication before chemotherapy.The patient experienced no acute side effects or complications in the chemotherapy unit. He was discharged home with an ambulatory 5-FU pump and was scheduled to return to the clinic at completion of his 5-FU infusion.Twenty-four hours later, the patient presented to the emergency department with new symptoms of erratic behaviour and confusion. Collateral history from the accompanying family members revealed that he had suffered a brief generalized tonic-clonic seizure earlier in the day, but no apparent history of head injuries, infectious symptoms, or recent alcohol intake was On examination in the emergency department, the patient was neither alert nor oriented. He was unable to follow commands, and his verbal responses were incomprehensible. He was agitated, and his limbs were tremulous at rest. Temperature was 35.9°C; heart rate, 82/min; respirations, 18/min; blood pressure, 130/84 mmHg; and O 2 saturation on room air, 99%. The patient's eyes appeared deviated to his left side, but pupils were equal and reactive. Spontaneous twitching of the extremities, on the left side more than on the right, was noted and attributed to possible complex partial seizures. No other focal neurologic deficits or evidence of trauma were present. The Brudzinski and Kernig signs were negative. Examinations of chest, heart, and abdomen were otherwise unremarkable. The patient was noted to be incontinent of urine during the assessment. He was treated with intravenous diazepam and phenytoin (given in a loading dose of 1000 mg) for his agitation and presumed seizure activity respectively. At this point, his 5-FU infusion pump was still attached and functioning.Laboratory investigations showed leucocytosis (white blood cell count: 19.5 ×10 9 /L) with left shift, but an otherwise normal complete blood cell count. Liver enzyme tests were within normal ...