A neonate with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) developed refractory hyponatremic seizures following administration of anticancer drugs. The seizures did not respond to diazepam, phenobarbital, or lidocaine, but resolved immediately with administration of phenytoin. The low water-excretion capacity in neonates should be taken into consideration when fluid loading is attempted, to avoid renal damage upon administration of drugs such as cisplatin that have a potential damaging effect on the kidney. Phenytoin could be the therapy of choice for SIADH and resulting seizures in the neonatal period.